the brain in dissociative identity disorder : reactions to ... · dissociative identity disorder...

Zurich Open Repository andArchiveUniversity of ZurichMain LibraryStrickhofstrasse 39CH-8057 Zurichwww.zora.uzh.ch

Year: 2013

The brain in dissociative identity disorder : reactions to subliminal facialstimuli and a task-free condition

Schlumpf, Yolanda R

Posted at the Zurich Open Repository and Archive, University of ZurichZORA URL: https://doi.org/10.5167/uzh-102276Dissertation

Originally published at:Schlumpf, Yolanda R. The brain in dissociative identity disorder : reactions to subliminal facial stimuliand a task-free condition. 2013, University of Zurich, Faculty of Arts.

The Brain in Dissociative Identity

Disorder: Reactions to Subliminal

Facial Stimuli and a Task-Free

Condition

Thesis

presented to the Faculty

of

Arts at the University of Zurich

for the degree of Doctor of Philosophy

by

Yolanda Schlumpf

of Mönchaltorf ZH, Switzerland

Accepted in the fall semester 2012

on the recommendation of

Prof. Dr. Lutz Jäncke

Prof. Dr. Björn Rasch

Zurich, 2013

Contents

Acknowledgments...................................................................................................... I

Summary ................................................................................................................... III

Zusammenfassung ..................................................................................................VII

Abbreviations............................................................................................................XI

1. Introduction .........................................................................................................1

2. Theoretical background .....................................................................................2 2.1. Dissociation and traumatizing events....................................................................2

2.2. The Theory of Structural Dissociation of the Personality....................................3 2.2.1. Supportive research findings: Reactions to supra- and subliminal threatening cues....4

2.3. The sociocognitive model of dissociative identity disorder ...............................5 2.3.1. Contradicting research findings: Suggestion, fantasy proneness, and role-playing......5

2.4. Resting-state functional magnetic resonance imaging in dissociative identity

disorder patients ................................................................................................................6

3. Methods ...............................................................................................................8 3.1. Participants...............................................................................................................8

3.2. Functional magnetic resonance imaging ..............................................................8 3.2.1. The basics of blood-oxygenation-level dependent imaging ..........................................8 3.2.2. Arterial spin labeling......................................................................................................9

3.3. Visual masking in functional magnetic resonance imaging..............................12

4. Aims and research questions..........................................................................16

5. Empirical part ....................................................................................................18 5.1. Experiment 1: Backward masking paradigm.......................................................18

5.1.1. Abstract .......................................................................................................................20 5.1.2. Introduction .................................................................................................................21 5.1.3. Methods and materials................................................................................................25 5.1.4. Results ........................................................................................................................32 5.1.5. Discussion...................................................................................................................39 5.1.6. Supplementary Findings .............................................................................................45

5.2. Experiment 2: Resting-state paradigm ................................................................47 5.2.1. Abstract .......................................................................................................................48 5.2.2. Introduction .................................................................................................................49 5.2.3. Methods ......................................................................................................................53 5.2.4. Results ........................................................................................................................57 5.2.5. Discussion...................................................................................................................62

6. General discussion...........................................................................................67 6.1. Summary of the results and embedding in the theoretical background..........67

6.1.1. Experiment 1 ...............................................................................................................67 6.1.2. Experiment 2 ...............................................................................................................68

6.2. Conclusion..............................................................................................................69

6.3. Implications and directions for future studies ....................................................69

References ...............................................................................................................71

Curriculum vitae ......................................................................................................84

I

Acknowledgments

I wish to express my thanks to all of those who helped me in accomplishing this work.

First of all I would like to thank my doctoral advisor Prof. Lutz Jäncke. He firstly

attracted my attention for neuroscience and gave me the opportunity to combine my

interest in clinical psychology with brain research methods. I am very grateful for his

scientific guidance and mentoring, and particularly for giving me the opportunity to

carry out this dissertation on a topic of my choice.

I would like to convey my gratitude to Dr. Ellert Nijehuis for his inspiration and the

enriching discussions of the clinical findings. I like to express further greatest thanks

to Dr. Simone Reinder who introduced me in a new field of research. Thank you both

for your effort and support.

This work would not have been possible without the professional clinical support of

Katharina Weder and Eva Zimmermann. I very appreciate the excellent cooperation

we had and the possibility to gain insights into the therapeutic work with dissociative

identity disorder patients.

I like to express great thanks to all coworkers and colleagues of the division of

Neuropsychology at the University of Zurich. I have truly enjoyed the friendly working

environment. I am very thankful for all fruitful discussions and instrumental supports. I

am especially grateful to my office colleague, Dr. Franciscus Liem, for the warm and

stimulating working atmosphere during my entire PhD period.

At this point, I would like to thank Prof. Dr. Björn Rasch for his unconditioned

acceptance to co-examine this dissertation.

I am indebted to Dr. Roger Lüchinger and Dr. Matthias Van Osch for their willingness

to support me and their patience in coaching me MR physics.

II

Special thanks go to the patients and their therapists. I am deeply impressed by their

motivation and effort to participate in the study. I appreciate very much their

confidence and the experiences I made during the measurements.

I express my gratitude to the financial support of the University of Zurich

(Forschungskredit), which made possible the study presented in this work.

Finally, I would like to express a very special thank to all my friends for keeping faith

in me and to my neighbours for the relaxing dinners. My deepest thanks go to my

family for their love and support.

III

Summary

Dissociative identity disorder (DID) is the most complex dissociative disorder. The

prevalence of DID in community samples is estimated to be between 0.4% (Akyuz,

Dogan, Sar, Yargic, & Tutkun, 1999) and 1.5% (Johnson, Cohen, Kasen, & Brook,

2006). The prevalence in samples of psychiatric patients ranges from approximately

1% (Gast, Rodewald, Nickel, & Emrich, 2001; Rifkin, Ghisalbert, Dimatou, Jin, &

Sethi, 1998) and 2% (Friedl & Draijer, 2000), to 5.4% (Tutkun, et al., 1998) and 6%

(Foote, Smolin, Kaplan, Legatt, & Lipschitz, 2006).

Proponents of the traumagenic view state that DID develops in the context of

severe and chronic trauma, often beginning in the early childhood (Dalenberg, et al.,

2012; Dell, 2006; Gleaves, 1996; Lyons-Ruth, Dutra, Schuder, & Bianchi, 2006;

Nijenhuis, Van der Hart, & Steele, 2002, 2004; Ogawa, Sroufe, Weinfield, Carlson, &

Egeland, 1997; Trickett, Noll, & Putnam, 2011; Van der Hart, Nijenhuis, & Steele,

2006). According to this view, the Theory of Structural Dissociation of the Personality

(TSDP) (Nijenhuis & Den Boer, 2009; Nijenhuis, et al., 2002; Van der Hart, et al.,

2006) proposes that DID is a severe form of posttraumatic stress disorder (PTSD)

and encompasses different types of dissociative parts of the personality. A primary

classification is “Emotional Part” (EP) and “Apparently Normal Part” (ANP). Switching

between these dissociative parts is a major characteristic of DID. Clinical

observations suggest that as EP, DID patients recall traumatic experiences and are

fixated on these memories. As ANP, DID patients claim a degree of amnesia for

trauma memories and are detached from the trauma.

A previous symptom-provocation study demonstrated that ANP and EP in DID

have different psychophysiological and neural reaction patterns to personalized

trauma scripts (Reinders, et al., 2003; Reinders, Nijenhuis, et al., 2006). In this study,

as EP compared to ANP, DID patients were psychophysiologically aroused and

showed significant activation in many brain areas also observed in PTSD patients

while they were confronted with a personalized trauma script. In contrast, as ANP,

DID patients yielded a brain activation pattern similar to patients with

depersonalization disorder and PTSD patients with negative dissociative symptoms

to trauma-related stimuli. Thus, in line with the hypotheses derived from the TSDP,

IV

as EP, patients were emotionally engaged in the trauma script, and as ANP, these

patients were detached from the trauma-related stimulus.

Whereas most theories of DID include traumatization as one of the causal

factors of the disorder, the sociocognitive model of DID entails the idea that the

disorder is caused by suggestion, fantasy proneness, and role-playing (Giesbrecht,

Lynn, Lilienfeld, & Merckelbach, 2008; Lilienfeld, et al., 1999; Lynn, Lilienfeld,

Merckelbach, Giesbrecht, & Van der Kloet, 2012; Merckelbach, Horselenberg, &

Schmidt, 2002; Merckelbach & Muris, 2001; Merskey, 1992; Piper & Merskey, 2004;

Spanos, 1994). Inconsistent with this view, DID patients were not particularly fantasy

prone, and low and high fantasy prone healthy participants did not generate the

patterns of psychophysiological and neural activation that marked these parts in DID

(Reinders, Willemsen, Vos, Den Boer, & Nijenhuis, 2012).

Two experiments were conducted as a part of the present work. Both focused

on the investigation of ANP and EP in DID patients as two prototypical dissociative

parts of the personality. The current thesis addressed the questions of whether ANP

and EP process threatening stimuli differently already at a preconscious level and,

furthermore, whether perfusion differences between ANP and EP exist in a task-free

condition (i.e., resting-state).

In Experiment 1, 15 female DID patients and 15 matched, mentally healthy,

female actors (controls) were confronted with masked (i.e., subliminally presented)

neutral and angry faces while their brain function was monitored using functional

magnetic resonance imaging (fMRI). Both, DID patients and actors, underwent

consecutively subliminal face presentation once as ANP and once as EP. Actors

were instructed and motivated to mimic these dissociative parts of the personality in

order to involve a psychobiological comparison between genuine and simulated DID

patients. The faces were presented for 16.7 msec, and a mask proceeded and

followed face presentation and ensured that the faces could not be seen consciously.

Each mask contained a colored dot (yellow or turquoise). The color of the dot on the

masks that preceded the faces was different from the color of the dot on the masks

that followed these pictures. The participants were instructed to immediately press a

button when they noticed that the color of the dot had changed, and their reaction

times (RTs) were measured. The longer RTs for the patients’ EP compared to the

patients’ ANP indicate that as EP, DID patients were fixated on the subliminally

V

presented faces. The longest RTs could be observed in EP following neutral faces

and are in line with the neural data showing the most prominent finding in the neutral

face condition aswell. EP in DID compared to EP in actors showed increased activity

as reaction to neutral faces in face-sensitive areas (i.e., occipito-temporal junction)

and in the dorsal brainstem. These findings indicate that as EP, DID patients deeply

engaged in subliminally presented faces, particularly in neutral faces, and were

psychophysiologically aroused by these faces. EP’s activity in motor-related areas

(i.e., pre-supplementary motor area, precentral gyrus) furthermore suggests

defensive reactions to perceived threat. As ANP, DID patients were associated with

less brain activity all over the brain in both face conditions, which suggests less

involvement in the subliminally presented faces. As predicted by the TSDP, actors

were not able to mimic DID patients neither as ANP nor as EP in a behavioral and

neural sense.

Based on these findings, a major clinical implication is that therapists of DID

patients must be emotionally and behaviorally engaged, as therapeutic neutrality

might scare the patient, particularly as EP, and might trigger defensive and emotional

reactions.

Experiment 2 consisted of the same sample as Experiment 1. In Experiment 2,

the subjects’ resting-state function as ANP and EP was recorded using an arterial

spin labeling (ASL) MR sequence. In this task-free condition, brain activation patterns

in DID were dependent on the type of dissociative part that was dominant during the

measurement. Compared to ANP, EP showed increased perfusion in the postcentral

gyrus (i.e., somatosensory cortex), dorsomedial prefrontal cortex, and motor-related

areas (i.e., pre-supplementary motor area, precentral gyrus, posterior midcingulate

cortex). This perfusion pattern suggests that as EP compared to ANP, DID patients

were attending more to their self-state and somatosensory sensations, which might

have triggered defense motor reactions. As ANP compared to EP, patients yielded

elevated bilateral thalamus activity, which is in line with previous studies showing that

negative dissociative symptoms are related to increased thalamic functioning. Fitting

their reported role-playing strategies, actors activated brain structures involved in

visual mental imagery and empathizing feelings.

In conclusion, the findings of Experiment 1 and Experiment 2 are consistent

with the TSDP and inconsistent with the idea that DID is caused by suggestion,

VI

fantasy proneness, and role-playing, as actors were not able to mimic the patterns of

brain function typically exhibited by DID patients.

VII

Zusammenfassung

Die dissoziative Identitätsstörung (DIS) ist die schwerste dissoziative Störung. Die

Prävalenz der DIS in der Normalbevölkerung liegt zwischen 0.4% (Akyuz, et al.,

1999) und 1.5 % (Johnson, et al., 2006). Die Prävalenz in klinischen Stichproben

reicht von ca. 1% (Gast, et al., 2001; Rifkin, et al., 1998) und 2% (Friedl & Draijer,

2000) bis 5.4% (Tutkun, et al., 1998) und 6% (Foote, et al., 2006).

Anhänger der traumabedingten Sichtweise behaupten, dass die Entstehung

einer DIS auf schwere und chronische Traumatisierungen, meistens beginnend in der

frühen Kindheit, zurückzuführen ist (Dalenberg, et al., 2012; Dell, 2006; Gleaves,

1996; Lyons-Ruth, et al., 2006; Nijenhuis, et al., 2002, 2004; Ogawa, et al., 1997;

Trickett, et al., 2011; Van der Hart, et al., 2006). In Übereinstimmung mit dieser

Sichtweise geht die Theorie der Strukturellen Dissoziation der Persönlichkeit (TSDP)

(Nijenhuis & Den Boer, 2009; Nijenhuis, et al., 2002; Van der Hart, et al., 2006)

davon aus, dass die DIS eine schwere Form einer posttraumatischen

Belastungsstörung (PTBS) ist und mit unterschiedlichen Arten von dissoziativen

Persönlichkeitsanteilen einhergeht. Eine grundlegende Unterscheidung besteht

zwischen dem “Emotionalen Persönlichkeitsanteil” (EP) und dem “Anscheinend

Normalen Persönlichkeitsanteil” (ANP). Der Wechsel zwischen diesen dissoziativen

Persönlichkeitsanteilen stellt ein Hauptmerkmal der DIS dar. Klinische

Beobachtungen legen nahe, dass DIS-Patienten als EP über ein Traumagedächtnis

verfügen und auf diese traumatischen Erinnerungen fixiert sind. Als ANP hingegen

weisen DIS-Patienten eine vollständige oder partielle Amnesie bezüglich

traumatischer Erfahrungen auf oder erleben diese als nicht zu ihnen gehörig.

In einer Symptomprovokationsstudie konnte gezeigt werden, dass DIS-

Patientinnen als ANP und EP unterschiedliche psychophysiologische und neuronale

Muster als Reaktion auf invidualisierte Trauma-Skripts aufweisen (Reinders, et al.,

2003; Reinders, Nijenhuis, et al., 2006). In dieser Studie waren DIS-Patientinnen als

EP im Vergleich zum ANP psychophysiologisch erregt und zeigten eine erhöhte

Aktivierung in Gehirnarealen, die auch bei PTBS-Patienten bei der Konfrontation mit

individualisierten Traumaskripts beobachtet werden konnte. Im Gegensatz dazu

zeigten DIS-Patientinnen als ANP ein Gehirnaktivierungsmuster, welches demjenigen

von Patienten mit einer Depersonalisationsstörung und PTBS-Patienten mit

VIII

negativen dissoziativen Symptomen als Reaktion auf Traumastimuli glich. Somit ist

festzuhalten, dass in Übereinstimmung mit den Hypothesen, die basierend auf der

TSDP formuliert wurden, Patientinnen als EP emotional in die Traumaskripts

involviert waren, währenddessen diesselben Patientinnen als ANP die Traumastimuli

als nicht zu sich gehörig verarbeiteten.

Während die meisten Theorien zur DIS davon ausgehen, dass

Traumatisierungen dieses Störungsbild verursachen, basiert das soziokognitive

Modell auf der Behauptung, dass die DIS durch Suggestion, Fähigkeit zum

Fantasieren und Rollenspiel erklärt werden kann (Giesbrecht, et al., 2008; Lilienfeld,

et al., 1999; Lynn, et al., 2012; Merckelbach, Horselenberg, et al., 2002; Merckelbach

& Muris, 2001; Merskey, 1992; Piper & Merskey, 2004; Spanos, 1994). Im

Widerspruch zu dieser Sichtweise konnte beobachted werden, dass DIS-

Patientinnen keine erhöhte Neigung zum Fantasieren aufweisen, und dass weder

gesunde Probandinnen mit einer tiefen noch mit einer hohen Neigung zum

Fantasieren die psychophysiologischen und neuronalen Reaktionsmuster von echten

DIS-Patientinnen hervorrufen konnten (Reinders, et al., 2012).

Im Rahmen dieser Arbeit wurden zwei Experimente durchgeführt. Beide

verfolgten das Ziel, ANP und EP als zwei prototypische dissoziative Anteile der

Persönlichkeit von DIS-Patientinnen zu erforschen. So ging die vorliegende

Doktorarbeit den Fragen nach, ob ANP und EP bedrohliche Stimuli bereits auf einer

vorbewussten Ebene unterschiedlich verarbeiten und ob Unterschiede in der

Gehirndurchblutung zwischen ANP und EP in einem Setting ohne externe

Aufgabenstellung (Ruhezustand) beobachted werden können.

In Experiment 1 wurden 15 DIS-Patientinnen und 15 parallelisierte, psychisch

gesunde Schauspielerinnen mit maskierten (d.h. subliminal präsentierten) neutralen

und wütenden Gesichtern konfrontiert. Während der subliminalen

Gesichterpräsentation wurde die Gehirnaktivierung mittels funktioneller

Magnetresonanztomographie (fMRT) aufgezeichnet. Sowohl die DIS-Patientinnen als

auch die Schauspielerinnen durchliefen das Experiment einmal als ANP und einmal

als EP. Die Schauspielerinnen wurden instruiert und motiviert, diese dissoziativen

Persönlichkeitsanteile zu imitieren, um echte und simulierte DIS-Patientinnen auf

psychobiologischer Ebene miteinander vergleichen zu können. Die Präsentationszeit

der Gesichter betrug 16.7 Millisekunden. Eine Maske wurde sowohl unmittelbar vor,

IX

als auch unmittelbar nach den subliminalen Gesichtern eingeblendet und

bewerkstelligte, dass die Gesichter nicht bewusst wahrgenommen werden konnten.

Auf jeder Maske war ein farbiger Punkt (gelb oder türkis) zu sehen. Die Farbe des

Punktes auf den Masken, die vor den Gesichtern gezeigt wurden, war jeweils eine

andere als die Farbe des Punktes auf den Masken, die auf diese Bilder folgten. Die

Teilnehmerinnen wurden dahingehend instruiert, so schnell wie möglich eine Taste

zu drücken, sobald sie einen Farbwechsel bemerkten. Dabei wurden ihre

Reaktionszeiten gemessen. Die Patientinnen zeigten als EP im Vergleich zum ANP

längere Reaktionszeiten, was darauf hinweist, dass die DIS-Patientinnen als EP auf

die subliminal präsentierten Gesichter fixiert waren. Die längsten Reaktionszeiten

konnten beim EP in der neutralen Gesichtsbedingung beobachtet werden. Dieser

Befund steht in Übereinstimmung mit den neuronalen Daten, da auf neuronaler

Ebene der bedeutendste Befund ebenfalls in der neutralen Gesichtsbedingung

beobachtet werden konnte. DIS-Patientinnen wiesen als EP im Vergleich zu

simulierten EPs in Reaktion auf neutrale Gesichter eine erhöhte Aktivierung in

Arealen auf, die an der Gesichtswahrnehmung beteiligt sind (occipito-temporaler

Übergangsbereich). Ebenso konnte eine erhöhte Aktivierung im dorsalen Hirnstamm

beobachtet werden. Diese Befunde weisen darauf hin, dass DIS-Patientinnen als EP

intensiv in die subliminal präsentierten Gesichter, insbesondere in neutrale Gesichter,

involviert waren und durch diese Gesichter psychophysiologisch erregt wurden. Des

Weiteren kann die Aktivierung der EPs in motorischen Arealen (prä-supplementär

motorisches Areal, präzentraler Gyrus) als Verteidigungsreaktion auf

wahrgenommene Bedrohung interpretiert werden. Als ANP zeigten DIS-Patientinnen

in beiden Gesichtsbedingungen eine generell niedrigere Aktivierung im ganzen

Gehirn. Dies lässt vermuten, dass Patientinnen als ANP weniger in die subliminal

präsentierten Gesichter involviert waren. Wie auf der TSDP basierend vorhergesagt

gelang es den Schauspielerinnen weder als ANP noch als EP nicht, die DIS-

Patientinnen auf behavioraler und neuronaler Ebene zu imitieren.

Eine wichtige therapeutische Implikation dieser Befunde ist, dass Therapeuten

von DIS-Patienten eine emotionale und verhaltensmässige Beteiligung ausdrücken

sollten, da therapeutische Neutralität die Patienten, und hierbei insbesondere als

EPs, verängstigen könnte. Und dies könnte wiederum Verteidigungs- und emotionale

Reaktionen auslösen.

X

Experiment 2 wurde mit der gleichen Stichprobe wie in Experiment 1

durchgeführt. In Experiment 2 wurden die Teilnehmerinnen als ANP und EP im

Ruhezustand mit einer Arterial Spin Labeling (ASL) MR-Sequenz gemessen. Die

Ergebnisse dieses Experimentes weisen darauf hin, dass in einem Setting, in der

keine externe Aufgabenstellung vorhanden ist, das Gehirnaktivierungsmuster von

DIS-Patientinnen von der Art des dissoziativen Persönlichkeitsanteils abhängt, der

während der Messung anwesend ist. Im Vergleich zum ANP zeigte der EP erhöhte

Durchblutung im postzentralen Gyrus (somatosensorischer Kortex), dosomedialen

präfrontalen Kortex und in Motorarealen (prä-supplementär motorisches Areal,

präzentraler Gyrus, posteriorer midzingulärer Kortex). Dieses Durchblutungsmuster

lässt vermuten, dass DIS-Patientinnen als EP im Vergleich zum ANP stärker mit der

Beobachtung ihres eigenen Zustandes und den somatosensorischen Empfindungen

beschäftigt waren, was möglicherweise zur Auslösung von motorischen

Verteidigungsreaktionen führte. Als ANP im Vergleich zum EP zeigten die

Patientinnen eine erhöhte bilaterale Thalamusaktivität. Dieser Befund deckt sich mit

früheren Studien, in denen ebenfalls negative dissoziative Symptome mit einer

erhöhten Thalamusfunktion einhergingen. Schauspielerinnen aktivierten

Gehirnstrukturen, die mit visueller Vorstellung und empathischem Einfühlen

assoziiert werden können. Dieses Aktivierungsmuster steht in Übereinstimmung mit

den von den Schauspielerinnen zur Ausübung des Rollenspiels berichteten

Strategien.

Zusammenfassend kann festgehalten werden, dass es Schauspielerinnen

nicht gelungen ist, die Funktionsweise des Gehirns von DIS-Patientinnen zu

imitieren. Die Ergebnisse von Experiment 1 und Experiment 2 stehen mit der TSDP

in Übereinstimmung, widersprechen jedoch der Idee, dass die DIS durch Suggestion,

Fähigkeit zum Fantasieren oder Rollenspiel erklärt werden kann.

XI

Abbreviations

A Angry faces

AB Attentional bias

aMCC Anterior midcingulate cortex

ANP Apparently Normal Part of the personality

ASL Arterial spin labeling

BOLD Blood-oxygenated-level dependent

CON Control group

CONanp Simulated ANP

CONep Simulated EP

DID Dissociative identity disorder/Patient group

DIDanp Genuine ANP

DIDep Genuine EP

DMN Default mode network

DMPFC Dorsomedial prefrontal cortex

dPCC Dorsal posterior cingulate cortex

EP Emotional Part of the personality

fMRI Functional magnetic resonance imaging

GM Gray matter

kE Cluster size

MNI Montreal Neurological Institute

MNS Mirror neuron system

N Neutral faces

OFC Orbitofrontal cortex

PET Positron Emission Computed Tomography

PCC Posterior cingulate cortex

pMCC Posterior midcingulate cortex

PTSD Posttraumatic stress disorder

Pre-SMA Pre-supplementary motor area

rCBF Regional cerebral blood flow

RT Reaction time

XII

S Scramble stimuli

SPECT Single Photon Emission Computed

Tomography

STS Sulcus temporalis superior

TSDP Theory of Structural Dissociation of the

Personality

Type Type of dissociative part of the personality

Introduction

1

1. Introduction

Dissociative identity disorder (DID) is the most complex and severe dissociative

disorder and is characterized by the appearance of severe dissociative symptoms,

such as amnesia, derealisation, depersonalisation, identity confusion, and identity

alteration (ISSD, 1997). The prevalence of DID in community samples is estimated to

be between 0.4% (Akyuz, et al., 1999), 1.1% (Sar, Akyuz, & Dogan, 2007), and 1.5%

(Johnson, et al., 2006). The prevalence rates for DID found in samples of psychiatric

patients ranged from approximately 1% (Gast, et al., 2001; Rifkin, et al., 1998) and

2% (Friedl & Draijer, 2000), to 5.4% (Tutkun, et al., 1998) and 6% (Foote, et al.,

2006). DID has gained a lot of attention for over more than a century, and is

increasingly acknowledged as a diagnostic entity. Although there is a growing

research literature, neuroimaging studies in DID are sparse, and there is still much

unknown about the neural mechanisms involved in DID.

This thesis focuses on several aspects of functional magnetic resonance

imaging to investigate neurophysiological characteristics of single dissociative parts

of the personality in DID. After a short introduction in chapter 1, chapter 2 addresses

the question what dissociation is and outlines two opposing theories of the aetiology

of DID. This chapter also summarizes previous research, which was derived from the

two models. Based on these theoretical and empirical grounds, the investigation of

the sense of self in DID is discussed. Chapter 3 describes the study sample and

gives a short introduction into the methods used in the experiments conducted as a

part of the present doctoral thesis. Chapter 4 outlines the aims of Experiment 1 and

Experiment 2 and emphasizes the relevance of this thesis. The two experiments

including the results are described in chapter 5, and chapter 6 concludes the thesis

with a summary of the results and a general discussion.

Theoretical background

2

2. Theoretical background

2.1. Dissociation and traumatizing events

Several theories have proposed that complex dissociative disorders, such as DID,

tend to develop in the context of severe and chronic childhood traumatization, which

includes chronic neglect and abuse by significant others. Numerous independent

studies support this view. For example, relations between attachment disruption and

dissociation two decades later have been documented (Dutra, Bureau, Holmes,

Lyubchik, & Lyons-Ruth, 2009; Lyons-Ruth, et al., 2006; Ogawa, et al., 1997), and in

many retrospective studies (Dell & O'Neil, 2009; Gleaves, 1996; Nijenhuis, 2004; Van

der Hart, et al., 2006), relations between chronic traumatization in childhood and DID

have been found. Reported traumatization in DID has been verified in a substantial

number of cases (Lewis, Yeager, Swica, Pincus, & Lewis, 1997). Many definitions of

dissociation have been proposed, and it was commonly defined as an important

survival mechanism, which provides a strategy of storing trauma-related knowledge

in a state-dependent manner. But no consensus on the phenomena has been

reached so far. To resolve the current conceptual confusion regarding dissociation

arising out of trauma, a new definition has been proposed (Nijenhuis & Van der Hart,

2011):

Dissociation in trauma entails a division of an individuals’s personality, that is,

of the dynamic, biopsychosocial system as a whole that determines his or her

characteristic mental and behavioural actions. This division of personality

constitutes a core feature of trauma. It evolves when the individual lacks the

capacity to integrate adverse experiences in part or in full, can support

adaptation in this context, but commonly also implies adaptive limitations. The

division involves two or more insufficiently integrated dynamic but excessively

stable subsystems. These subsystems exert functions, and can encompass

any number of different mental and behavioural actions and implied states.

These subsystems and states can be latent, or activated in a sequence or in

parallel. Each dissociative subsystem, that is, dissociative part of the

personality minimally includes its own, at least rudimentary first-person

perspective. As each dissociative part, the individual can interact with other


3

dissociative parts and other individuals, at least in principle. Dissociative parts

maintain particular psychobiological boundaries that keep them divided, but

that they can in principle dissolve. Phenomenologically, this division of the

personality manifests in dissociative symptoms that can be categorized as

negative (functional losses such as amnesia and paralysis) or positive

(intrusions such as flashbacks or voices), and psychoform (symptoms such as

amnesia, hearing voices) or somatoform (symptoms such as anesthesia or

tics). (p. 418)

This definition stresses the lack of integration within the personality due to potentially

traumatizing events, which overwhelm or lower the exposed individuals’ integrative

capacity. The definition goes beyond the idea that dissociation is a simple protective

mechanism. In contrast to the dissociative parts of the personality who can be

characterized by negative dissociative symptoms, those who manifest positive

dissociative symptoms are completely exposed to re-experiencing the traumatic past.

2.2. The Theory of Structural Dissociation of the Personality

The hypotheses of the present study are derived from the Theory of Structural

Dissociation of the Personality (TSDP) (Nijenhuis & Den Boer, 2009; Nijenhuis, et al.,

2002; Van der Hart, et al., 2006). According to this theory, DID involves different

types of dissociative, that is, insufficiently integrated subsystems or parts of the

personality as a whole biopsychosocial system. The basic structural trauma-related

dissociation is between the “Emotional Part” (EP) and “Apparently Normal Part”

(ANP). ANP is largely mediated by evolutionary prepared action systems for

functioning in daily life. As ANP, DID patients may claim a degree of amnesia for

traumatic memories, do not or not sufficiently personify traumatic experiences and

memories, and attempt to mentally and behaviorally avoid trauma-related stimuli.

They are to some degree depersonalized and bodily numbed, thus, ANP can be

associated with negative dissociative symptoms. In contrast, EP is primarily mediated

by action systems for bodily defense to potential threat and can be distinguished in

subtypes (Nijenhuis & Den Boer, 2009). One subtype is fixed in traumatic memories

and engages in active mammalian defenses to a major threat (e.g., freeze, flight,


4

attachment cry). In response to perceived or real threat, they manifest strong

emotional and sensorimotor reactions (i.e., hyperarousal), which can be described as

positive dissociative symptoms. The other subtype engages in passive mammalian

defense (playing dead), which implies emotional and bodily anesthesia. In the two

experiments included in this present dissertation, we only investigated the former

subtype, which will be referred to as EP in the rest of the text.

According to the TSDP (Van der Hart, et al., 2006), dissociative disorders can

be described on a continuum from simple forms to complex forms of dissociative

disorders. In primary structural dissociation, which is characteristic of posttraumatic

stress disorder (PTSD) and simple forms of somatoform dissociative disorders (i.e.,

dissociative disorders of sensation and movement), there is one ANP and one EP.

Secondary structural dissociation, which marks complex PTSD and many cases of

dissociative disorder not otherwise specified (DDNOS), involves one ANP and

multiple EPs. Tertiary structural dissociation is the organization characterizing DID

and encompasses multiple ANPs and multiple EPs.

2.2.1. Supportive research findings: Reactions to supra- and subliminal

threatening cues

A previous Positron Emission Computed Tompgraphy (PET) study shows strong

evidence that ANP and EP can be associated with different physiological and neural

patterns as reaction to trauma-related cues (Reinders, et al., 2003; Reinders,

Nijenhuis, et al., 2006). In this study, DID patients listened as ANP and EP to

audiotaped descriptions of a traumatic memory that was only autobiographical for

EP. The findings support the hypotheses derived from the TSDP that as EP, DID

patients are fixed in traumatic memories and have hyperaroused psychobiological

reactions to reminders of traumatic experiences, and that as ANP, they react to

trauma-related cues in a depersonalized and detached manner (i.e., hypoarousal).

The study of Reinders et al. (2003) and Reinders, Nijenhuis et al. (2006) will be

described in more details in the empirical part (chapter 5).

A second study used backward masking (i.e., masked/subliminal presentation

of emotional facial stimuli) to address the question of whether these differences

between ANP and EP already exist at a preconscious level (Hermans, Nijenhuis, Van

Honk, Huntjens, & Van der Hart, 2006). ANP and EP were for 25 msec exposed to


5

neutral faces and angry faces (i.e., potent conditioned threat stimuli after sexual and

physical abuse). They were instructed to mention the color of the masks following the

faces. ANP but not EP showed a significantly shorter reaction time (RT) in color

naming the masks that followed the angry faces compared to masks that followed the

neutral faces. This RT pattern indicates that ANP but not EP engages in

preconscious mental avoidance of perceived threat.

The automaticity of phobic responses in PTSD patients has been documented

in imaging studies using backward masking of trauma-related stimuli (Armony,

Corbo, Clement, & Brunet, 2005; Bryant, et al., 2008; Hendler, et al., 2003; Rauch, et

al., 2000). Experiment 1, conducted as a part of the present dissertation (see chapter

5), is the first research project that used this paradigm to examine neural activity in

DID patients in response to fear-related stimuli presented below the threshold of

conscious awareness. The backward masking technique will be described in more

detail in the method section (chapter 3).

2.3. The sociocognitive model of dissociative identity disorder

A rival theory to the TSDP is the sociocognitive theory of DID, which holds that DID

involves fantasy proneness, suggestibility, and role-enactment rather than a history

of childhood trauma (Giesbrecht, et al., 2008; Lilienfeld, et al., 1999; Lynn, et al.,

2012; Merckelbach, Horselenberg, et al., 2002; Merckelbach & Muris, 2001; Merskey,

1992; Piper & Merskey, 2004; Spanos, 1994). This assumption is related to the

iatrogenic position. Iatrogenic proponents assert that DID is a creation of (possibly

suggestive) psychotherapeutic treatment inducing false memories (Piper & Merskey,

2004). In this view, the psychotherapist plays a critical role, and DID is not regarded

as a valid psychiatric disorder.

2.3.1. Contradicting research findings: Suggestion, fantasy proneness, and

role-playing

Nijenhuis and Reinders found that women with DID are less fantasy prone than

patients with borderline personality disorder and not more fantasy prone than female

high school students, university teachers, and university personnel (Reinders, et al.,

2012). Reinders et al. (2012) also observed that neither high nor low fantasy prone


6

mentally healthy women who were instructed and motivated to simulate ANP and EP

convincingly mimicked the reaction patterns of ANP and EP in women with DID in a

psychophysiological and neural sense. In the Hermans et al. (2006) study, described

above, healthy controls instructed to role-play ANP and EP showed the reverse RT

patterns compared to ANP and EP of genuine DID patients. That is, as ANP, the

actors tended to react like EP in DID patients, and as EP like ANP in these patients.

In line with the TSDP, these findings show strong evidence that DID cannot be

explained by suggestion, fantasy proneness, or role-playing. Nevertheless, fantasy

proneness and applied fantasy can play a role in the development of phenomenal

self-models of dissociative parts (e.g., the idea of a dissociative part of a female

patient that he is male) (Nijenhuis and Reinders, see Supporting Information S1 to

Reinders, et al., 2012).

To date, no study could prove that traumatic memories can be experimentally

induced. Research and clinical observations support the hypothesis that traumatic

memories have a poor narrative quality, are nonverbal and fragmentary in nature,

and strongly involve sensorimotor features (Brewin, 2001; Van der Kolk, 1997).

Findings of false memory studies conducted so far (Loftus, Coan, & Pickrell, 1996;

Loftus & Ketcham, 1994; Loftus & Pickrell, 1995) are restricted to manipulations of

narrative memories (i.e., explicit verbal memories) and, thus, cannot be generalized

to the sensorimotor and highly emotional trauma memories of DID patients.

Furthermore, authors theoretically strongly biased against the existence of DID have

not done a single study with DID patients. Their findings rely on self-reports of

students (Merckelbach, Muris, Rassin, & Horselenberg, 2000; Merckelbach, Rassin,

& Muris, 2000) and psychiatric patients suffering from other mental disorders

(Merckelbach, à Campo, Hardy, & Giesbrecht, 2005).

2.4. Resting-state functional magnetic resonance imaging in dissociative

identity disorder patients

According to the TSDP (Van der Hart, et al., 2006), dissociative parts of the

personality include at least a rudimentary form of first-person perspective. This

perspective pertains to the subjective feeling of being an acting and experiencing self

with an outward perspective of the perceived world and an inward perspective


7

regarding oneself (Metzinger, 2003). The question of self-consciousness and self-

referencing has occupied the minds of philosophers and psychologists for centuries.

And recently, this topic has also been discussed in neuroscience (Northoff, et al.,

2006). There is an emergent body of evidence in brain imaging research that a

specific set of brain regions consisting of the medial prefrontal cortex (MPFC),

posterior cingulate (PCC) in addition to midline parietal structures, lateral parietal

regions, and medial and lateral temporal lobes is engaged during rest (Buckner,

Andrews-Hanna, & Schacter, 2008; Gusnard & Raichle, 2001; Raichle, et al., 2001).

There is substantial overlap between this default mode network (DMN) and the

network involved in self-referential processes. For instance, activity in the DMN has

been shown in tasks involving autobiographical memory retrieval (Andreasen, et al.,

1995; Svoboda, McKinnon, & Levine, 2006) and mind wandering or spontaneous

thoughts (Andrews-Hanna, Reidler, Huang, & Buckner, 2010; Christoff, Gordon,

Smallwood, Smith, & Schooler, 2009; Mason, et al., 2007). This might not be

surprising as a task-free condition such as resting-state allows individuals to think to

themselves undisturbed.

Resting-state imaging studies can help to increase our knowledge of neural

mechanisms underlying the phenomenal self-models in DID. On the other hand,

research in DID can be of major value in comprehending self-referential processes in

general by experimentally controlling and inducing dissociative parts (i.e., ANP and

EP). In Experiment 2 described in chapter 5 (empirical part), we conducted a resting-

state experiment with DID patients and actors mimicking DID.

Methods

8

3. Methods

3.1. Participants

The two experiments included in this present dissertation were carried out on the

same samples of subjects. Fifteen female outpatients who met the DSM-IV

(American Psychiatric Association, 1994) criteria for DID were enrolled in the study,

and each DID patient was measured as ANP and EP. Therefore, a major inclusion

criteria was the ability to alternate between ANP and EP at request and to remain

activated, particularly as EP, for a substantial period of time in the scanner. Fifteen

DID-simulating actors (matched in age and educational level with the DID group)

were included as controls to test the claim that DID involves suggestion and role-

playing. They were instructed and motivated to create an ANP and EP and to

practice simulating these parts before the measurement. The instructions included a

video showing a DID patient alternating between ANP and EP and detailed written

information on the TSDP (Van der Hart, et al., 2006). Further details on the study

sample will be discussed in the empirical part (chapter 5).

3.2. Functional magnetic resonance imaging

Functional magnetic resonance imaging (fMRI) is currently the most widely used

method for studying neural processes in the human brain. The physical principles on

which fMRI is based are complex, and a thorough discussion of them is beyond the

scope of this thesis. Therefore, only the basic concepts will be briefly described.

Functional MRI can be used to map activated brain regions. The fMRI signal

constitutes an indirect measurement based on the strong relationship of neural

activity and neurovascular properties (Logothetis, Pauls, Augath, Trinath, &

Oeltermann, 2001). Two different techniques, which can be employed to assess

diverse aspects of the haemodynamic response, will be discussed in the following.

3.2.1. The basics of blood-oxygenation-level dependent imaging

The blood-oxygenation-level dependent (BOLD) signal exploits the fact that

oxygenated and deoxygenated blood have different magnetic properties (Pauling &

Coryell, 1936; Thulborn, Waterton, Matthews, & Radda, 1982) -- oxygenated blood

Methods

9

(oHBO2) is paramagnetic, whereas deoxygenated blood (dHBO2) is dimagnetic.

When a brain region is neurally activated it consumes oxygen causing an initial

decrease of oxyhemoglobin. After this initial dip (Malonek & Grinvald, 1996), the

supply of oxygenated blood is higher as the actual need, which increases the ratio

between oxygenated and deoxygenated blood (Fox & Raichle, 1986), and leads to a

higher fMRI signal. In this context, deoxyhemoglobin can be considered as a form of

endogenous tracer for measuring brain activity (Ogawa, Lee, Kay, & Tank, 1990).

The temporal resolution of the BOLD signal in the range of sec is poor. The peak of

the signal is reached approximately after 5 sec from stimulus onset and returns after

10 to 16 sec back to baseline. In contrast to the low temporal resolution, a good

spatial resolution (approximately 2-3 mm) is achieved (Jäncke, 2005). The BOLD

response ends with a post-stimulus undershoot. The mechanism of this undershoot

is still unresolved (Van Zijl, Hua, & Lu, 2012). Figure 1 depicts the time course of the

BOLD signal change.

-10! -5! 0! 5! 10! 15! 20! 25!

Time in sec!

Initial dip! Under-shoot!

Peak!

Stim

ulu

s!

Figure 1. Time course of the BOLD signal.

3.2.2. Arterial spin labeling

With arterial spin labeling (ASL) perfusion MRI, brain perfusion can be noninvasively

measured at rest and with task activation. This cerebral blood flow (CBF) reflects the

volume of flow per unit brain mass per unit time and is expressed in physiological

units of mL/g/min. In gray matter (GM), a typical value is roughly 60mL/100g/min

Methods

10

(Buxton, 2002). In ASL, arterial blood water is magnetically labeled using

radiofrequency (RF) pulses. In contrast to CBF measurements in PET, no exposure

to ionizing radiation is required (Detre, et al., 1994). The inverted spins in the blood

water flow into the slice of interest in the brain, which leads to a reduction in total

tissue magentization and, as a consequence, to a decline in the MR signal and image

intensity. During this time, an image is taken (called the label image). To create

another image (called control image), the experiment is then repeated without

labeling the arterial blood. The label image and the control image are acquired in an

interleaved fashion. Pairwise subtraction of label and control images yields a

difference image, which has an intensity proportional to CBF (Wolf & Detre, 2007).

Figure 2 describes schematically this ASL acquisition procedure.

Figure 2. Basic concept of ASL perfusion MRI. Taking the difference of the control and label images yields an image (ΔM = M control – M label) that is proportional to CBF.

A mean perfusion CBF image is generated by averaging all difference images

per subject. An example of such a CBF map is depicted in Figure 3.

Methods

11

0

0.5

1

1.5

2

2.5

3x 10

4

Figure 3. Example of a CBF map in 23 slices of a human brain (created in MATLAB, http://www.mathworks.ch/products/matlab). Color scale from blue to red indicates perfusion intensity.

Perfusion based fMRI has not received that much attention than imaging

sequences based on the BOLD contrast. The main disadvantage of ASL compared to

BOLD is the poor signal to noise ratio (SNR) of the ASL response -- typically less

than half that of the BOLD response (Liu & Brown, 2007). The time between the

labeling and image acquisition (i.e., delay time) is about one second corresponding to

1 mL of blood delivered to 100 mL of tissue (see above). This means that the

inflowing blood magnetization constitutes only about 1% of the total signal, the rest

being the tissue (Liu & Brown, 2007). In addition, the image coverage in ASL

methods is inferior to that of BOLD with ASL studies typically acquiring a smaller

number of slices and thicker slices compared to BOLD studies (Liu & Brown, 2007).

Futhermore, the ASL effects are measured through comparison of label and control

images, which means the temporal resolution is low because of the need to acquire

two sets of images (Liu & Brown, 2007). Temporal resolution is further diminished by

the time that is needed to let the labeled blood flow into the imaging region.

Nevertheless, ASL provides a variety of advantages compared to BOLD

studies. BOLD signal changes are a result of an interaction between a number of

physiological variables including CBF, cerebral blood volume (CBV), and oxygen

utilization. Consequently, BOLD signal changes are expressed as a relative

percentage signal change compared to a baseline, as they cannot be quantified in

physiological units, and a change in the BOLD signal is not easy to interpret, as it can

be related to age or disease that cause changes in any of these physiological

variables (D'Esposito, Deouell, & Gazzaley, 2003). In contrast, ASL provides a

Methods

12

quantitative CBF measurement, and is therefore useful in the investigation of

individual differences in brain metabolism. This is particularly beneficial for clinical

neuroscience studies, as normal and patient populations can be compared in terms

of an absolute quantitative perfusion measurement (Detre, Rao, Wang, Chen, &

Wang, 2012). Furthermore, ASL is known to better reflect neural activity as compared

to BOLD (Liu & Brown, 2007). The BOLD signal requires venous blood, which can

contribute to activation-induced susceptibility changes, as it contains

deoxyhemoglobin (Ogawa, et al., 1993). In contrast, the ASL perfusion signal is

restricted to the capillary bed and, therefore, offers a measurement, which is well

localized to the part of the vascular system where neural activity takes place (Liu &

Brown, 2007). In addition, pairwise subtraction between adjacently acquired label and

control images dramatically changes the noise of the ASL signal (i.e., baseline drifts,

motion artefacts) compared to the BOLD signal (Wong, 1999; Zarahn, Aguirre, &

D'Esposito, 1997). Independent studies have demonstrated that inter-subject and

inter-session variability is decreased in ASL measures compared to BOLD (Aguirre,

Detre, Zarahn, & Alsop, 2002; Tjandra, et al., 2005; Wang, et al., 2003). Moreover,

the ability to use imaging sequences (e.g., spin-echo) that are insensitive to

susceptibility effects reduce susceptibility-related signal losses (Liu & Brown, 2007).

Taken together, ASL methods are quantitative and stable over time and

therefore most useful for longitudinal or multisite studies (Wolf & Detre, 2007).

3.3. Visual masking in functional magnetic resonance imaging

Masking can be used to manipulate perceptual awareness of visual stimuli. In

backward masking, a target picture is shown briefly (i.e., subliminally) and is

immediately followed by another masking stimulus to preclude conscious awareness

of the target picture (Öhman, 2002; Wiens & Öhman, 2002). However, an aversively

conditioned masked target can induce emotional reactions from subjects without

being consciously perceived (Öhman & Soares, 1994). Therefore, backward masking

is a powerful technique for studying preconscious (i.e., pre-attentive, automatic)

processing of threatening stimuli in an fMRI setting.

In Experiment 1, backward masking was applied. The paradigm of this

experiment will be described in detail in chapter 5 (empirical part), and only a short

Methods

13

overview is given in this section. Facial expressions are one of the most intensively

studied objects in the emotion literature. We used neutral and angry faces from the

Karolinska set (Karolinska Directed Emotional Faces (KDEF)) and included

approximately half male and half female subjects (Lundquist, Flykt, & Öhman, 1998).

Angry faces can be regarded as potent conditioned threat stimulus after sexual and

physical abuse. Scrambled stimuli served as a baseline condition and were also

presented subliminally (presentation time 16.7 msec). Black-and-white dotted masks

immediately preceded and followed the subliminal stimuli and ensured that they could

not be seen consciously. Figure 4 depicts the stimulus material and a schematic

representation of the masking paradigm. A beamer (digital light processing, DLP)

projected the stimuli on a half-transparent screen, which could be seen via a mirror

system placed on the head coil.

Figure 4. Experimental design. (A) Example stimuli (KDEF, identity number M12 and M30 (Lundquist, et al., 1998)) and visual noise mask. (B) Schematic representation of the masking paradigm.

Each mask contained a colored dot (yellow or turquoise). The color of the dot

on the masks that preceded the experimental pictures was different from the color of

the dot on the masks that followed these pictures. The participants were instructed to

immediately press a button when they noticed that the color of the dot had changed.

This button press task (based on Reinders, et al. (2005) and Reinders, Glascher, et

neutral! angry! scramble! mask!

(A)!

Methods

14

al. (2006)) was used to measure condition-dependent RTs. An attentional bias (AB)

score was calculated by subtracting the mean value of the RTs related to scrambled

stimuli from the mean value for the RTs related to neutral and related to angry faces,

respectively. A positive AB score (i.e., longer RTs for facial stimuli than scrambled

stimuli) can be interpreted as vigilance, and a negative one (i.e., longer RTs for

scrambled stimuli than facial stimuli) as avoidance (Bakvis, et al., 2009; Putman,

Hermans, & Van Honk, 2004; Van Honk, et al., 1998, 2000).

In masking paradigms, it is essential to check explicitly if the target pictures

have been presented below the threshold of conscious awareness, and there are two

general approaches to the valid measurement of the level of awareness (Cheesman

& Merikle, 1984). The subjective approach employs a subjective report or “claimed

unawareness” measure. Participants were as ANP and EP invited to report what they

saw on the screen during the fMRI measurement. The objective approach defines

unawareness in terms of performance on tasks that measure perceptual

discrimination. We used a two-alternative forced-choice test. Following the fMRI

measurement, a set of faces was presented masked again. After the subliminal

presentation of each face, we supraliminally projected this target face together with a

randomly chosen face matched in sex and emotional expression, and requested the

participants to say or guess which of these two faces had been previously projected

subliminally. If the mean of hits is approximately 50%, the level of detectability is at

chance level (Kihlstrom, Barnhardt, & Tataryn, 1992), and it can be assumed that the

participants had not consciously seen the experimental faces.

We also examined the projector’s capacity, using a light sensor, to project

pictures subliminally (see Figure 5). The sensor was fixed on the screen while the

computer was running a sequence of alternating black-and-white images with a

presentation time of 16.7 msec. The sensor’s output was measured by a digital

oscilloscope. The actual presentation time of the projector was around 16.5 msec ± 2

msec. It thus projected the subliminal pictures within the critical time limit.

Methods

15

Figure 5. Examination of the projector’s capacity: Light sensor, oscilloscope, and the oscilloscope’s output.

Light sensor! Oscilloscope! Output! light sensor! oscilloscope! output!

Aims and research questions

16

4. Aims and research questions

The principal purpose of the present work is to contribute to a better understanding of

underlying neural mechanisms of DID. Psychobiological research of DID is

particularly sparse, and the number of studies addressing DID is disproportionally low

to the substantial prevalence rates in DID (see above) and subjective and economical

costs associated with DID (Galbraith & Neubauer, 2000). The TSDP (Van der Hart, et

al., 2006) provides testable hypotheses about dissociative reactions in response to

various situations. In this context, prior studies investigating the neurophysiological

underpinnings of DID might have failed to find significant differences between two

dissociative parts, as they involved an ANP/ANP or EP/EP rather than an ANP/EP

comparison (Coons, Milstein, & Marley, 1982; Hughes, Kuhlman, Fichtner, &

Gruenfeld, 1990; Sar, Unal, Kiziltan, Kundakci, & Ozturk, 2001). This thesis focuses

on the investigation of ANP and EP in DID patients as two prototypical dissociative

parts of the personality.

Aims and research questions of Experiment 1: To assess preconscious

processing of perceived threat in ANP and EP of DID patients and to compare these

reaction patterns with actors who were instructed and motivated to simulate ANP and

EP. The motivation for these aims is based on previous research demonstrating that

ANP and EP in DID patients have different behavioral and psychobiological reactions

to supraliminal and subliminal trauma-related cues and that controls instructed and

motivated to simulate ANP and EP in DID were unable to mimic these reaction

patterns (Hermans, et al., 2006; Reinders, et al., 2003; Reinders, Nijenhuis, et al.,

2006; Reinders, et al., 2012).

In line with the TSDP (Van der Hart, et al., 2006) and the previous empirical

findings, we hypothesized that ANP preconsciously mentally avoids neutral and

angry masked faces, whereas EP is fixed in the faces. We speculated that the

differences between ANP and EP are correlated with neural activity associated with

disengagement and engagement in subliminal facial expressions and RTs indicating

avoidance (i.e., negative AB score) and vigilance (i.e., positive AB score) of the

involved faces. We also predicted that these differences are more pronounced

Aims and research questions

17

following angry compared to neutral faces. We furthermore hypothesized that actors

have different behavioral and psychobiological reactions to the subliminal faces.

Aims and research questions of Experiment 2: To test the hypotheses that ANP

and EP in DID patients have different perfusion patterns in response to rest

instructions, and that perfusion is different in ANP and EP simulating actors. Previous

studies (Hermans, et al., 2006; Reinders, et al., 2003; Reinders, Nijenhuis, et al.,

2006) provided insights into dissociative part-dependent reactions to trauma-related

stimuli. The present experiment extends the investigation to a task-free condition.

We hypothesized that in response to rest instructions, ANP and EP in DID

have different patterns of brain perfusion and that comparisons of ANP and EP

simulating controls yield different neural reactivity patterns than comparisons of ANP

and EP in DID patients. We predicted that DID patients show relatively higher

activation in areas which commonly exhibit increased neural activity following rest

instructions (default mode activity), and that controls elicit a brain pattern distinct from

the default mode activity because simulating an ANP and EP and being a genuine

ANP and EP constitute different mental states.

Empirical part: Experiment 1

18

5. Empirical part

5.1. Experiment 1: Backward masking paradigm

Dissociative part-dependent biopsychosocial reactions to backward masked

angry and neutral faces: An fMRI study of dissociative identity disorder

Published in NeuroImage: Clinical 3 (2013) 54-64

Authors:

Yolanda R. Schlumpf, MSca, Ellert R.S. Nijenhuis, PhDb, Sima Chalavi, MScc,

Ekaterina V. Weder, MScd, Eva Zimmermann, MSce, Roger Luechinger, PhDf,

Roberto La Marca, PhDg, A.A.T. Simone Reinders, PhDc,h, Lutz Jäncke, PhDa,i

a Division of Neuropsychology, Institute of Psychology, University of Zurich, Switzerland

b Top Referent Trauma Center Mental Health Care Drenthe, Assen, The Netherlands

c Department of Neuroscience, University Medical Center Groningen, and BCN Neuroimaging Center,

University of Groningen, Groningen, The Netherlands

d Private practice, Eschen, Liechtenstein

e Fribourg General Hospital, Fribourg, Switzerland

f Institute for Biomedical Engineering, University and ETH Zurich, Switzerland

g Division Clinical Psychology and Psychotherapy, Institute of Psychology, University of Zurich,

Switzerland

h Department of Psychosis Studies, Institute of Psychiatry, King’s College London, London, United

Kingdom

i International Normal Aging and Plasticity Imaging Center, University of Zurich, Switzerland

Keywords: dissociative identity disorder, neuroimaging, backward masking, face

perception, emotional ambiguity, hypervigilance

Acknowledgments: This research was supported by the Forschungskredit of the

University of Zurich. A.A.T.Simone Reinders is supported by the Netherlands

Organization for Scientific Research (www.nwo.nl), NWO-VENI grant no. 451-07-009.

We would like to thank the colleagues of Prof. Jäncke’s lab for their helpful comments


19

and Franz Liem and Thomas Reber for their technical support. Special thanks go to

the patients and their therapists for participating in the study.


20

5.1.1. Abstract

Objective: The Theory of Structural Dissociation of the Personality (TSDP) proposes

that dissociative identity disorder (DID) patients are fixed in traumatic memories as

“Emotional Parts” (EP), but mentally avoid these as “Apparently Normal Parts” of the

personality (ANP). We tested the hypotheses that ANP and EP have different

biopsychosocial reactions to subliminally presented angry and neutral faces, and that

actors instructed and motivated to simulate ANP and EP react differently.

Methods: Women with DID and matched healthy female actors (CON) were as ANP

and EP (DIDanp, DIDep, CONanp, CONep) consecutively exposed to masked

neutral and angry faces. Their brain activation was monitored using functional

magnetic resonance imaging. The black-and-white dotted masks preceding and

following the faces each had a centered colored dot, but in a different color.

Participants were instructed to immediately press a button after a perceived color

change. State anxiety was assessed after each run using the STAI-S. Final statistical

analyses were conducted on 11 DID patients and 15 controls for differences in neural

activity, and 13 DID patients and 15 controls for differences in behavior and

psychometric measures.

Results: Differences between ANP and EP in DID patients and between DID and

CON in the two dissociative parts of the personality were generally larger for neutral

than for angry faces. The longest reaction times (RTs) existed for DIDep when

exposed to neutral faces. Compared to DIDanp, DIDep was associated with more

activation of the parahippocampal gyrus. Following neutral faces and compared to

CONep, DIDep had more activation in the brainstem, face-sensitive regions, and

motor-related areas. DIDanp showed a decreased activity all over the brain in the

neutral and angry face condition. There were neither significant within differences nor

significant between group differences in state anxiety. CON was not able to simulate

genuine ANP and EP biopsychosocially.

Conclusions: DID patients have dissociative part-dependent biopsychosocial

reactions to masked neutral and angry faces. As EP, they are overactivated, and as

ANP underactivated. The findings support TSDP. Major clinical implications are

discussed.


21

5.1.2. Introduction

Dissociative Identity Disorder (DID) is the most complex of dissociative disorders

(American Psychiatric Association, 1994). According to the Theory of Structural

Dissociation of the Personality (TSDP) (Nijenhuis, et al., 2002; Van der Hart, et al.,

2006), DID is a severe form of posttraumatic stress disorder (PTSD) encompassing

different types of dissociative parts of the personality. In TSDP, personality is

understood as a whole biopsychosocial system, and dissociative parts as

subsystems of this whole system. Van der Hart et al. (2006) propose a distinction

between “Emotional Parts” (EP) and “Apparently Normal Parts” (ANP) of the

personality. DID involves more than one EP and more than one ANP. Switching

between these dissociative parts is a major characteristic of DID. EP is fixed in

traumatic memories. As ANP, DID patients may claim a degree of amnesia for these

memories, do not or not sufficiently personify traumatic experiences and memories,

and attempt to mentally avoid trauma-related stimuli. TSDP distinguishes different

prototypical subtypes of EP (Nijenhuis & Den Boer, 2009). Some subtypes show

strong emotional reactions to trauma-related stimuli and engage in active mammalian

defensive reactions (e.g., freeze, flight, attachment cry), whereas another subtype

engages in passive mammalian defense (playing dead), which implies emotional and

bodily anesthesia.

Severe and chronic dissociative symptoms tend to develop in the context of

severe and chronic childhood traumatization, which includes profound attachment

disruptions (Dalenberg, et al., 2012; Diseth, 2006; Nijenhuis & Den Boer, 2009;

Nijenhuis, et al., 2002; Ogawa, et al., 1997; Trickett, et al., 2011). In a Positron

Emission Tomography (PET) study, female DID patients listened as ANP and as EP

(in Reinders, Nijenhuis, et al. (2006) referred to as a neutral identity state (NIS) and

trauma-related identity state (TIS)) to autobiographical neutral and trauma scripts

while their psychophysiological and brain activation was monitored (Reinders, et al.,

2003; Reinders, Nijenhuis, et al., 2006). As ANP, the patients in this study reacted

similarly to the neutral and the trauma memory scripts. This finding suggests low

emotional involvement in trauma-related stimuli, which is consistent with TSDP. In

this study, EP (subtype active defense), as compared to the ANP, showed significant

activation of many areas also observed in PTSD patients while being confronted with

a personalized trauma script (Lanius, et al., 2001; Rauch, et al., 1996; Shin, et al.,


22

2001). EP but not ANP demonstrated strong psychophysiological reactions to the

trauma script. Thus, EP but not ANP was psychobiologically aroused. ANP showed a

brain activation pattern similar to patients with depersonalization disorder (Simeon, et

al., 2000) and PTSD patients with negative dissociative symptoms to trauma-related

stimuli (Lanius, Bluhm, Lanius, & Pain, 2006; Lanius, et al., 2002).

According to the sociocognitive view (also referred to as fantasy model

(Dalenberg, et al., 2012)), DID is caused by high fantasy proneness, role-playing,

suggestibility, and iatrogenic suggestion (Giesbrecht, et al., 2008; Lilienfeld, et al.,

1999; Merckelbach, Devilly, & Rassin, 2002; Merckelbach & Muris, 2001; Merskey,

1992; Spanos, 1994). Few suggestions would suffice to generate dissociative parts in

suggestible, fantasy prone individuals (Spanos, 1996). However, a recent symptom

provocation functional brain imaging study provided evidence suggesting that DID is

not linked to fantasy proneness. Reinders et al. (2012) found that neither high nor low

fantasy prone mentally healthy women instructed and motivated to simulate ANP and

EP were able to enact the psychophysiological and neural activation patterns of the

genuine ANP and EP.

A study by Hermans et al. (2006) used backward masking to expose DID

patients to angry and neutral faces for 25 msec. Attentional bias scores were

calculated by subtracting the reaction times (RTs) needed to color-name the mask

that immediately followed a neutral face from the RTs needed to color-name the

mask that immediately followed an angry face. A positive attentional bias score (i.e.,

longer RT for angry than neutral faces) was interpreted as vigilance, and a negative

one (i.e., longer RT for neutral than angry faces) as avoidance (Bakvis, et al., 2009;

Putman, et al., 2004; Van Honk, et al., 1998, 2000). Hermans et al. (2006) found that

as ANP but not as EP, DID patients had a negative attentional bias in that their RT to

angry faces was faster than that to neutral faces. Healthy controls instructed and

motivated to role-play ANP and EP did not show this negative bias. Taken together,

these behavioral data also contradict the sociocognitive view of DID.

The findings from Reinders et al. (2003, 2012), Reinders, Nijenhuis et al.

(2006), and Hermans et al. (2006) support the hypotheses derived from TSDP that as

EP engaging in active defense, DID patients are fixed in traumatic memories and

demonstrate unusually strong cortical, subcortical and vegetative reactions (i.e.,

hyperarousal) to reminders of traumatic experiences. As ANP on the other hand, they


23

react to trauma-related cues in a depersonalized and detached manner (i.e.,

hypoarousal). In addition, these differences between ANP and EP exist already at a

preconscious level, that is, with respect to pre-attentive reactivity to external and

internal stimuli.

EP’s preconscious fixation on perceived threat (Hermans, et al., 2006) is

hypothesized to be associated with neural networks related to perceptual and

emotional processing of the angry faces. Reactions to emotional faces compared to

neutral faces are expected to be associated with greater activation in early visual

areas (striate cortex) and higher order visual areas (extrastriate cortex) including

face-sensitive regions in the fusiform gyrus (Vuilleumier & Pourtois, 2007). Functional

imaging studies have identified additional areas in the extrastriate occipito-temporal

region involved in the visual analysis of faces (i.e., lateral inferior occipital cortex,

sulcus temporalis superior [STS]) (Haxby, Hoffman, & Gobbini, 2000). Amaral and

colleagues have demonstrated that enhanced activity within the visual cortex as

reaction to emotional stimuli is mainly driven by the amygdala, which has strong

anatomical connections to visual areas (Amaral, Price, Pitkanen, & Carmichael,

1992). One of the main contributions of the amygdala is to support rapid reaction to

potential or actual sources of danger (Davis & Whalen, 2001; LeDoux, 1998; Phan,

Wager, Taylor, & Liberzon, 2002). Activity within the amygdala can occur even if the

threatening stimuli are presented below the level of awareness (Morris, Ohman, &

Dolan, 1998; Whalen, et al., 1998). Amygdala responsitivity and associated vigilance

are abnormally enhanced in PTSD (Armony, et al., 2005; Rauch, et al., 2000; Shin, et

al., 2004). This hypervigilance fits clinical observations that as EP engaged in active

defense, patients are continuously scanning the environment for threat cues.

Engagement in active defense may thus be associated with enhanced activation in

motor-related areas, which was found in the study of Reinders, Nijenhuis et al. (2006)

as well (i.e., basal ganglia, cerebellum). This proposal also fits the observations that

the cortical motor system is activated during emotional processing in humans

(Hajcak, et al., 2007; Oliveri, et al., 2003), which prepares the individual for an

appropriate motor reaction (Baumgartner, Willi, & Jancke, 2007).

In most previous functional imaging studies with masked stimuli investigating

PTSD patients, the analysis was mainly restricted to the amygdala as a key brain

structure for emotional processing (Armony, et al., 2005; Hendler, et al., 2003;


24

Rauch, et al., 2000). This focus on the amygdala reflected a particular a priori interest

in the role of this brain structure in fear. However, Sakamoto and colleagues

conducted a whole-brain analysis (Sakamoto, et al., 2005). In this study, PTSD

patients showed significantly higher activations to masked traumatic images in the

left parahippocampal gyrus and the tail of the left hippocampus.

Per definition neutral faces do not express a clear emotion, thus can be

perceived as emotionally ambiguous. Like anxiety disorder patients, and consistent

with clinical observations, as EP, DID patients may have difficulty tolerating

uncertainty or ambiguity (Grillon, et al., 2008; Holaway, Heimberg, & Coles, 2006)

and may tend to interpret ambiguous stimuli in negative ways (Bishop, 2007;

Eysenck, Mogg, May, Richards, & Mathews, 1991).

The current functional magnetic resonance imaging (fMRI) study aims to

examine the underlying neural activation patterns involved in ANP-dependent and

EP-dependent preconscious reactivity. Based on the mentioned theoretical and

empirical grounds, we specifically hypothesized that compared to (i) ANP in DID

patients, and (ii) EP in controls, EP in DID patients have a different pattern of neural

activity in response to subliminally presented faces, particularly more activity in

primary and higher-order visual areas, face-sensitive areas including extrastriate

occipito-temporal regions, limbic structures including the amygdala and

hippocampal/parahippocampal region, and motor-related areas comprising the

cortical motor system, basal ganglia, and cerebellum. We also hypothesized that (iii)

these differences are more pronounced following angry faces, that (iv) EP in DID

patients have longer RTs to these faces than ANP in DID patients and than EP in

controls, and that (v) comparisons of ANP and EP in controls yield different neural

and behavioral reactivity patterns than comparisons of ANP and EP in DID patients.


25

5.1.3. Methods and materials

Participants

Fifteen female outpatients who met the DSM-IV American Psychiatric Association

(American Psychiatric Association, 1994) criteria for DID were enrolled in the study.

They were recruited from private practitioners of psychiatry and psychotherapy and

psychiatric outpatient departments in Switzerland and Germany. The clinical

diagnosis was independently checked by clinical experts in dissociative disorders (E.

Weder [EW] and E. Zimmermann [EZ]) using the German version of the Structured

Clinical Interview for DSM-IV Dissociative Disorders (SCID-D) (Steinberg, 1993), the

(SKID-D) (Gast, Hofmann, Oswald, & Zündorf, 2000). All patients had to be involved

in a treatment phase involving exposure to trauma-related memories (Steele, Van der

Hart, & Nijenhuis, 2005; Van der Hart, et al., 2006). Exclusion criteria were comorbid

psychosis, drug abuse or addiction, antisocial or histrionic personality disorder, and a

neurological or organic brain disease. Two patients were free of medication. All other

patients were medicated predominantly with antidepressant medication.

Fifteen female actors who were motivated to simulate ANP and EP served as

controls. They did not differ significantly from the patients in age (controls: M=43.2

years, SD=10.4; patients: M=43.3 years, SD=9.1; t(28)=0.019, p>.05) and

educational level (controls: M=4.7, SD=1.2; patients: M=4.1, SD=1.5; t(26.099)=-

1.341, p>.05; the educational level was assessed by a 7-point Likert scale based on

the common European educational system). The controls were interviewed by EW

and EZ using the SKID-D (Gast, et al., 2000). They also completed the German

version of the Posttraumatic Diagnostic Scale (PDS) (Ehlers, Steil, Winter, & Foa,

1996) and the Beck Depression Inventory II (BDI-II) (Hautzinger, Keller, & Kühner,

2006) to ensure that none of the controls had a dissociative disorder, PTSD, and/or

major depression. The actors watched a video showing a DID patient talking to her

therapist. In the video, the therapist invites the patient to alternate between ANP and

EP. Based on detailed written information on TSDP (Van der Hart, et al., 2006), the

actors were instructed and motivated to create an ANP and EP using a list of

properties (e.g., name, sex, age). ANP should be a dissociative part without

personalized memories of traumatizing events and EP as a dissociative part with

personalized traumatic memories. The actors were requested to practice simulating


26

ANP and EP as often as they deemed necessary to adequately enact these roles but

at least three times before the MRI measurement. Patients completed as ANP and

EP the State Anxiety Inventory (STAI-S) (Laux, Glanzmann, Schaffner, &

Spielberger, 1981) immediately after the fMRI measurement, as did the controls to

check if the actors had understood and followed the instructions to simulate an ANP

and EP.

Each subject was informed about risks and inconveniences associated with

the experiment before written informed consent was obtained. All procedures were

approved by the local ethical committee and were conducted in accordance with the

standards set by the Declaration of Helsinki. All participants received a financial

compensation of 80 Swiss Francs for their participation.

Stimuli and experimental design

A backward masking paradigm was used to investigate preconscious mental

reactivity to masked faces. The Karolinska Directed Emotional Faces (KDEF) served

as photographic stimuli. They involved neutral, happy, fearful, and angry facial

expressions, including approximately half male and half female subjects (Lundquist,

et al., 1998). The selection of the facial pictures used in the study was based on a

rating of the intensity and genuineness of the displayed emotions (Van Balen, 2005).

In addition to the faces, houses and scrambled images were presented. Scrambled

stimuli were created in Fourier space by setting a low level of phase-coherence

(Reinders, Den Boer, & Buchel, 2005; Reinders, Glascher, et al., 2006) in face

pictures and served as baseline stimuli. All pictures were matched for luminance,

contrast, brightness, and spatial frequency information (Rainer, Augath, Trinath, &

Logothetis, 2001; Reinders, et al., 2005; Reinders, Glascher, et al., 2006).

The pictures were generated by the software Presentation (version 14.1,

http://www.neurobs.com) on a computer (Intel Core 2 Duo CPK, 60-Hz refresh rate)

outside the scanner room. A DLP beamer (Plus U2-1110) projected them on a half-

transparent screen, which could be seen via a mirror system placed on the head coil.

All blocks of pictures were shown three times in a pseudorandomized order (18

blocks in total). Order effects were controlled by using two playlists (P1, P2), which

were randomly assigned to ANP and EP. Each block consisted of 10 subliminal


27

pictures (16.7 msec) and 11 black-and-white dotted masks (2.5 sec). The masks,

also used in previous studies (Henke, Mondadori, et al., 2003; Henke, Treyer, et al.,

2003), immediately preceded and followed the subliminal stimuli. This procedure

ensured that the pictures could not be consciously perceived. The duration of the

mask (equivalent to the interstimulus interval) was jittered by ± 1 sec in randomized

steps of 0.5 sec. Every block lasted for 27.5 sec and was separated by a 2.5 sec

mask (interblock interval), resulting in a total time of 9 min per run. Figure 6 depicts

the temporal sequence of events in a block.

Figure 6. Experimental design. Example stimuli (KDEF, identity number M14 and F20 (Lundquist, et al., 1998)), masks, and fixation dots are presented from one block displayed during the fMRI measurement.

A button press task (based on Reinders, et al. (2005) and Reinders, Glascher,

et al. (2006)) was used to measure condition-dependent RTs. Each mask contained

a colored dot (yellow or turquoise). The color of the dot on the masks that preceded

the experimental pictures was different from the color of the dot on the masks that

followed these pictures. The participants were instructed to immediately press a

button when they noticed that the color of the dot had changed. To direct the

participants’ gaze to the center of the faces, the dots on the masks were positioned

at the place that corresponded with the center between the eyebrows of the faces.

Each participant was first tested as ANP, and then as EP. The patient switched

between dissociative parts of the personality outside the scanner room with little

guidance from the research clinician. Inadvertent switches to a different dissociative

part than the intended ANP or EP during the fMRI measurement were checked by

asking the participants after the run what dissociative part had been present during


28

the run. If there had been a switch to or a co-activation of an unintended dissociative

part, the run was repeated, which was the case in one ANP and two EPs. A LED light

of the response box in the scanner room switched on and off in synchrony with the

participants’ button presses. The authors observed that irregular flashing of this light

was a good indicator of co-awareness of and/or switching to an unintended

dissociative part during the experiment in DID patients. DID patients behaving like

this explained that they had major difficulty to execute the button press task in an

adequate fashion. For example, they reported that an unintended dissociative part

wanted to participate in the task but was not or not fully aware of task instructions.

Therefore, the authors closely watched the regularity of the LED flashing. It appeared

that DID patients with irregular patterns of button presses were precisely the patients

who were removed from the statistical analysis for other methodological reasons (see

later).

Determination of awareness

The level of awareness of the masked images was determined at the very end of the

experiment, outside of the scanner, using a subjective and an objective test

(Cheesman & Merikle, 1984). The subjective test involves the participant’s self report.

Thus, the ANPs and EPs were asked what they had seen while lying in the scanner.

The objective test is a forced-choice task, and constitutes the ‘gold-standard’ for the

determination of awareness (Cheesman & Merikle, 1984; Greenwald, Draine, &

Abrams, 1996; Holender, 1986). The subjective and objective tests demonstrated

that the participants had not consciously seen the experimental images (see

Supplementary Findings 1 and Supplementary Table 1). A light sensor (Vishay

Semiconductors) was used to examine the beamer’s capacity to project pictures

within the refresh rate of the computer’s graphic card (NVIDIA Quadro FX 1700, 60-

Hz) (see Supplementary Findings 2).

Image acquisition and data preprocessing

Functional magnetic resonance imaging (fMRI) scanning was performed at the

University Hospital of Zurich with a 3-T Philips Achieva whole-body magnetic


29

resonance imaging equipped with an eight-channel Philips SENSE head coil. A total

of 325 T2*-weighted echo planar image volumes, with blood-oxygen-level-dependent

(BOLD) contrast (imaging parameter: echo time=30msec, repetition time=1.7sec, flip-

angle=79º, FOV=220x220x107mm, slice thickness=2.4mm, slice gap=1mm, acquired

voxel size=2.75x2.75x2.4mm, slices per volume=32, SENSE factor=2), were

acquired during a single run. Initial ‘dummy’ volumes were obtained to ensure BOLD

saturation. The data analysis was performed with the parametric mapping software

SPM8 (http://www.fil.ion.ucl.ac.uk/spm). Standard imaging pre-processing and

statistical analysis procedures were applied. To account for movement artifacts, the

functional images were realigned to the mean volume and coregistered onto the

subject specific T1 image. This T1 image was normalized using the unified

segmentation approach (Ashburner & Friston, 2005). The resulting normalization

matrix was applied to the functional volumes, which transformed them into MNI space

(new voxel size=2x2x2mm). Data were spatially smoothed with an 8-mm full width at

half-maximum (FWHM) Gaussian kernel. In line with the experimental design, the

BOLD data was modeled with a block design convolved with the standardized

canonical haemodynamic response function (HRF). In one ANP of a DID patient, we

observed huge imaging artifacts. One ANP of a DID patient reported that she had

fallen asleep during the measurement. For one patient’s EP, we found massive

movement artifacts and one patient’s EP was unable to complete the measurement.

In view of our repeated measures ANOVA, the data of these four patients were

omitted casewise. The final brain imaging statistical analysis was performed with

data of 11 participants in the patient group and 15 in the control group.

A model with six condition and six movement regressors (with the realignment

parameters) was aligned for each participant for ANP and EP separately at the first

level analysis. The current analyses are restricted to the contrasts Neutral-Scramble

(N-S) and Angry-Scramble (A-S). The results of the other contrasts will be published

elsewhere. At the second level, the data were analyzed using a factorial design that

consisted of two independent variables resulting in a 2×4 ANOVA with repeated

measures on the second factor: Group (two levels: DID/CON), Condition (four levels:

ANP N-S/ANP A-S/EP N-S/EP A-S). The analysis was based on a whole-brain voxel-

wise comparison. For the main effect of condition, main effect of group, and

interaction effect, we employed an uncorrected statistical threshold (i.e., voxel level of


30

significance uncorrected [unc.] for multiple testing for the whole brain) of p<.001 with

respect to our a priori defined regions. The selection of these regions is based on

previous studies outlined in the introduction section (Hajcak, et al., 2007; Haxby, et

al., 2000; Reinders, Nijenhuis, et al., 2006; Sakamoto, et al., 2005; Vuilleumier &

Pourtois, 2007; Whalen, et al., 1998). To avoid type-2 errors, statistical thresholds of

similar sizes have been used in affective and clinical neuroscience research

(Felmingham, et al., 2008; Phelps, et al., 2001). Where no a priori hypothesis was

available, we only accepted brain areas that reached a corrected p-value (p<.05).

Corrected p-values are reported based on the family-wise error (FWE) correction at

cluster level (Friston, Holmes, Poline, Price, & Frith, 1996; Friston, Worsley,

Frackowiak, Mazziotta, & Evans, 1994).

The participants were measured as ANP and EP in the patient group

(DIDanp/DIDep) and in the control group (CONanp/CONep). The following eight

planned comparisons were performed: DIDanp-DIDep N-S, CONanp-CONep N-S,

DIDanp-CONanp N-S, DIDep-CONep N-S, DIDanp-DIDep A-S, CONanp-CONep A-

S, DIDanp-CONanp A-S, DIDep-CONep A-S. Planned comparisons were not

orthogonal. Statistical thresholds for a priori defined regions for these planned

comparisons were adjusted for multiple testing using Bonferroni correction (p<.05/8=

p<.000125). All tests were one-sided, thus, were performed twice to assess positive

differences in the BOLD signal in one and in the inverse contrast. Again, where no a

priori hypothesis was available, we only accepted brain areas that survived FWE

correction at cluster-level (p<.05). A cluster-size threshold of 7 voxels was applied.

Only the first peak of a cluster and only the most significant finding of a brain area

are reported in the Table 2 to 5. The exact location of all clusters was defined using

the Harvard-Oxford cortical and subcortical structural atlases (Desikan, et al., 2006)

and by visual inspection on a high-resolution T1-weighted image in FSL

(http://www.fmrib.ox.ac.uk/fsl). The cingulate subregions were named according to

Vogt’s cytoarchitectonic division (Vogt, 2005).

Data analysis: behavioral reactions

An attentional bias (AB) score was calculated by subtracting the mean value of the

RTs for the three scrambled face blocks (S) from the mean value for the RTs of the


31

three neutral face blocks (N) and the angry face blocks (A), respectively. The data of

the participant who fell asleep and the one whose EP was not able to finish the

measurement were excluded. The final statistical analysis was performed with data

of 13 participants in the patient group and 15 in the control group. We calculated a

2×4 ANOVA with repeated measures on the second factor: Group (two levels:

DID/CON), Condition (four levels: ANP N-S/ANP A-S/EP N-S/EP A-S) in SPSS18.

For the main effect of condition, main effect of group, and interaction effect, p-values

were set at .05. The following eight planned comparisons were performed: DIDanp-

DIDep N-S, CONanp-CONep N-S, DIDanp-CONanp N-S, DIDep-CONep N-S,

DIDanp-DIDep A-S, CONanp-CONep A-S, DIDanp-CONanp A-S, DIDep-CONep A-

S. Planned comparisons were not orthogonal. Therefore, Bonferroni correction was

applied and p-values were set at .00625, one-tailed.

Furthermore, the following four post-hoc t-tests were calculated to ensure that

a RT difference can be explained by a face-specific effect: DIDanp N-S versus

DIDanp A-S, DIDep N-S versus DIDep A-S, CONanp N-S versus CONanp A-S,

CONep N-S versus CONep A-S. Bonferroni adjusted p-values were set at .0125,

one-tailed.

Data analysis: state anxiety

A total value of the STAI-S (sum of obtained scores in the questionnaire) was

calculated for each participant. The data of the participant who fell asleep and the

one whose EP was not able to finish the measurement were excluded. The final

statistical analysis was performed with data of 13 participants in the patient and 15 in

the control group.

We calculated a 2×2 ANOVA with repeated measures on the second factor:

Group (two levels: DID/CON), Type of dissociative part (two levels: ANP/EP) in

SPSS18. For the main effect of group, main effect of type of dissociative part, and

interaction effect p-values were set at .05.


32

5.1.4. Results

Behavioral data

There was a significant interaction effect of group by condition (F(1,26)=4.82, p<.05,

partial h2=.16). The main effect of group and the main effect of condition did not

reach a significant threshold (p>.05). In AB N-S, Bonferroni corrected planned

comparisons revealed a RT difference between DIDanp and DIDep (t(12)=-3.15,

p<.00625, d=1.31). In AB A-S, planned comparisons did not reveal any significant

results (p>.00625). Nevertheless, there is a clear positive AB N-S and a tendency to

a positive AB A-S in DIDep (Figure 7).

Figure 7. Mean attentional bias (AB) score (reaction times [RTs] for emotional faces minus RTs for scrambled faces) for (A) the neutral faces (AB N-S) and (B) the angry faces (AB A-S) in msec (±SEM). A positive AB indicates vigilance, a negative AB indicates avoidance, * p<.00625 (Bonferroni corrected).

We observed a significantly longer RT in DIDep N-S compared to DIDep A-S

(t(12)=2.69, p<.0125, d=0.73). All other post-hoc tests did not reach the critical

threshold (p>.0125). Figure 8 depicts the mean and standard error of RT (A-S) – (N-

S) in DIDanp, DIDep, CONanp, and CONep.


33

Figure 8. Mean reaction time (N-S)-(A-S) of ANP and EP in DID and CON (±SEM).

State anxiety

There was neither a significant main effect of group, nor a significant main effect of

type of dissociative part, nor an interaction effect of group by type of dissociative part

(p>.05). Table 1 summarizes the descriptive statistics of the STAI-S score in DIDanp,

DIDep, CONanp, and CONep.

Table 1. Descriptive statistics of state anxiety

STAI-S Mean SD

DID (n=13)

DIDanp 49.92 11.64

DIDep 52.90 14.83

CON (n=15)

CONanp 48.87 13.22

CONep 49.80 10.15

Note. STAI-S, state anxiety inventory; DIDanp, ANP DID group; DIDep, EP DID group; CONanp, ANP control group; CONep, EP control group


34

Neural data

Repeated measures ANOVA

We found a significant main effect of condition (putamen, posterior part of the

parahippocampal gyrus) and a significant interaction effect of group by condition

(parahippocampal gyrus, middle temporal gyrus) (Table 2). There was no significant

main effect of group.

Table 2. Main effect condition and interaction effect

MNI coordinatesa

Brain area Side x y z kE F value

Main effect condition Putamen L -24 6 0 73 8.70

Parahippocampal gyrus (posterior

part) R 18 -36 -10 33 7.90

Interaction effect Parahippocampal gyrus (anterior

part) R 16 -10 -24 29 9.60

Middle temporal gyrusb R 62 -38 -8 17 7.31

Note. R/L, left or right hemisphere; kE, cluster-size in voxels (one voxel is 2x2x2mm) a MNI coordinates (in mm) refer to the maximum of signal change in each region b ventral bank of the sulcus temporalis superior

Planned comparisons

Within-group comparisons of two different types of dissociative parts of the

personality (i.e., ANP-EP comparisons) are listed in Table 3. ANP-EP comparisons

between groups are given in Table 4 and 5.

Within-group ANP-EP comparisons

In the angry and neutral face condition, DIDep had more activation in the

parahippocampal gyrus than DIDanp (DIDep-DIDanp N-S/A-S, Table 3). This

activation was not found for ANP versus EP in controls. The neutral faces but not the

angry faces evoked a significantly increased right amygdala activity as well as in

several cortical regions in CONanp compared to CONep (CONanp-CONep N-S,

Table 3).


35

Table 3. ANP/EP effects within groups in response to masked angry and neutral faces as compared to scrambled faces (A-S, N-S)

MNI coordinatesa

Condition A-S Brain area Side x y z kE T value

DIDanp - DIDep n.s

DIDep - DIDanp Parahippocampal gyrus (anterior part) R 20 -14 -26 9 4.20

CONanp - CONep n.s.

CONep – CONanp n.s

Condition N-S

DIDanp - DIDep n.s

DIDep - DIDanp Parahippocampal gyrus (anterior part) R 16 -12 -26 11 4.27

CONanp - CONep Superior frontal gyrus L -20 28 54 140 4.94*

aMCC/pMCC R 2 12 36 277 4.65*

Precentral gyrus (premotor cortex) L -42 -4 46 25 4.26

Amygdala R 26 -6 -22 16 4.15

Middle temporal gyrus (temporooccipital

part) R 58 -56 2 7 4.03

CONep – CONanp n.s.

Note. R/L, left or right hemisphere; kE, cluster-size in voxels (one voxel is 2x2x2mm); n.s., not significant; DIDanp, ANP DID group; DIDep, EP DID group; CONanp, ANP control group; CONep, EP control group; aMCC, anterior midcingulate cortex; pMCC, posterior midcingulate cortex a MNI coordinates (in mm) refer to the maximum of signal change in each region * corrected for multiple comparisons using cluster-level statistics, p < .05

Between-group ANP-EP comparisons

In the angry face condition and compared to CONep, DIDep was associated with

more activation in the precentral gyrus (DIDep-CONep A-S, Table 4). In the neutral

face condition (DIDep-CONep N-S, Table 4), the same contrast demonstrated

increased neural activation for DIDep. Multiple large clusters reached our predefined

statistical thresholds. The first cluster with a peak value in the left dorsal brainstem

includes several mainly left lateralized areas in the occipito-temporal junction (lingual

gyrus, temporal occipital fusiform gyrus, and occipital fusiform gyrus) and the left

parahippocampal gyrus (Figure 9). Within this cluster, brainstem and lingual gyrus

survived FWE correction for whole-brain multiple comparisons (p<.05, Table 5).

DIDep had more activation in several a priori defined regions (middle temporal gyrus,


36

STS, lateral occipital cortex, occipital pole). As this type of dissociative part, DID

patients also had more activation in several motor-related areas (pre-supplementary

motor area, precentral gyrus).

x = -12 y = -58

Figure 9. Brain regions showing significantly higher activation during preconscious exposure to neutral faces as compared to scrambled faces in DIDep compared to CONep (DIDep-CONep, N-S). The saggital view depicts areas in the dorsal brainstem, occipitotemporal junction, and parahippocampal gyrus. Activation in the visual cortex can be seen in the coronal view. Corresponding regions, cluster-sizes, MNI coordinates, and t-values can be found in Table 4.


37

Table 4. ANP/EP effects between groups in response to masked angry and neutral faces as compared to scrambled faces (A-S, N-S)

MNI coordinatesa

Condition A-S Brain area Side x y z kE T value

DIDanp - CONanp n.s.

CONanp - DIDanp n.s

DIDep - CONep Precentral gyrus (primary motor cortex) L -36 -14 40 21 4.31

CONep - DIDep n.s.

Condition N-S

DIDanp - CONanp n.s.

CONanp - DIDanp n.s.

DIDep - CONep Brainstem (dorsal part)c

L -12 -26 -18 1729 5.44*

Parahippocampal gyrus (anterior part) R 16 -10 -24 35 5.29

Middle frontal gyrus R 40 32 32 267 5.26*

Middle frontal gyrus L -28 32 48 136 5.26*

Middle temporal gyrus

R 62 -38 -8 81 4.86*

Pre-SMA L -2 4 62 159 4.85*

Precentral gyrus (primary motor cortex) R 42 -10 44 386 4.83*

pMCC/dPCC 0 -26 32 274 4.74*

DMPFC R 2 56 24 166 4.53*

Middle temporal gyrusb

R 60 -22 -12 54 4.50

Precentral gyrus (primary/premotor

cortex) L -36 -14 42 46 4.34

STS L -58 -16 -6 13 4.32

Lateral occipital cortex (inferior part) R 54 -68 0 24 4.21

Occipital pole (peristriate cortex) R 28 -96 -2 7 4.12

CONep - DIDep n.s.

Note. R/L, left or right hemisphere; kE, cluster-size in voxels (one voxel is 2x2x2mm); n.s., not significant; DIDanp, ANP DID group; DIDep, EP DID group; CONanp, ANP control group; CONep, EP control group; Pre-SMA, pre-supplementary motor area; pMCC, posterior midcingulate cortex; dPCC, dorsal posterior cingulate cortex; DMPFC, dorsomedial prefrontal cortex; STS, sulcus temporalis superior a MNI coordinates (in mm) refer to the maximum of signal change in each region b ventral bank of the sulcus temporalis superior c cluster includes Brainstem R, Parahippocampal gyrus L, Lingual gyrus R/L, Temporal occipital fusiform gyrus L, Occipital fusiform gyrus L * corrected for multiple comparisons using cluster-level statistics, p < .05


38

Table 5. Dissociative-part effects between groups in response to masked neutral faces as compared to scrambled faces (N-S)

MNI coordinatesa

Condition N-S Brain area Side x y z kE T value

DIDep - CONep Brainstem L -12 -26 -18 42 5.44**

Middle frontal gyrus R 40 32 32 35 5.26**

Note. R/L, left or right hemisphere; kE, cluster-size in voxels (one voxel is 2x2x2mm); DIDep, EP DID group; CONep, EP control group a MNI coordinates (in mm) refer to the maximum of signal change in each region ** FWE correction for whole-brain multiple comparisons, p < .05 (kE = 7)


39

5.1.5. Discussion

This is the first fMRI study of neural activation patterns to preconsciously perceived

facial expressions for two different prototypes of dissociative parts of the personality

(ANP and EP) in DID patients. As generally hypothesized, we found different neural

and behavioral activation patterns for ANP and EP in DID patients and in controls.

Consistent with our first hypothesis, as EP, DID patients demonstrated more

activation in the right parahippocampal gyrus during the masked presentation of

neutral and angry faces than they had as ANP (see Table 3). The parahippocampal

gyrus has been implicated in recall of autobiographical memories (Fink, et al., 1996),

with a right hemispheric predominance (Tulving, Kapur, Craik, Moscovitch, & Houle,

1994), and in re-experiencing symptoms in PTSD (Osuch, et al., 2001; Sakamoto, et

al., 2005). The observed enhanced activation in the parahippocampal gyrus

corresponds with core features of EP, that is, their fixation in traumatic memories,

their tendency to perceive safe individuals as dangerous, and their tendency to

reactivate traumatic memories when confronted with reminders of traumatic

experiences. However, we did not find the hypothesized differences for ANP and EP

in DID patients with respect to visual areas, face sensitive areas, amygdala, and

motor areas. This negative finding may at least in part relate to limitations of the

present study, which will be discussed below.

Differences in neural activation patterns were much more pronounced for EP

in DID patients compared to EP in controls. But in contrast with our third hypothesis,

EP’s subliminal perception of neutral and not angry faces revealed these strong

differences. In reaction to subliminally presented angry faces, EP in DID showed

enhanced activity in the precentral gyrus (see Figure 9). We also observed

increased activity in the temporal pole of the superior temporal gyrus. This area is

known to participate in the analysis of faces too, particularly in processing the

semantic knowledge of a face (Haxby, et al., 2000). We are reluctant to discuss this

activity any further, as it did not reach the statistical threshold for non-a priori defined

regions. Masked neutral faces evoked activation in a cluster of brain areas including

the dorsal brainstem, parahippocampal gyrus, and mainly left lateralized areas

positioned in the occipito-temporal junction (see Figure 9), as well as several motor-

related areas (see Table 4).


40

Taken together, the findings of the current study suggest that as EP, DID

patients deeply engaged in subliminally presented faces, particularly in neutral faces.

DIDep’s dorsal brainstem activity furthermore indicates increased arousal (Jones,

2003) and associated vigilance in reaction to subliminally perceived neutral faces.

The occipito-temporal junction is a face-sensitive region (Gorno-Tempini, et

al., 2001; Haxby, et al., 2000; Nakamura, et al., 2000), and the occipital fusiform

gyrus contributes at a very early phase in the face-processing stream and generates

the initial representation of a face (Pitcher, Walsh, Yovel, & Duchaine, 2007). The

mainly left lateralized activation pattern is in line with previous findings of left

hemispheric involvement in subliminal perception of faces (Henke, Landis, &

Markowitsch, 1994). Activation of motor areas could indicate defensive reactions to

perceived threat.

Given the integral role of the amygdala in automatic processing of threatening

stimuli (Öhman, 2005; Vuilleumier, 2005), the reason for the lack of amygdalar

activity in our study deserves a closer look. PTSD neuroimaging studies have led to

inconsistent findings with regards to amygdala activation. Studies employing masked-

faces paradigm (Rauch, et al., 2000) or visual imagery (Shin, et al., 1997)

demonstrated exaggerated amygdala responses in PTSD patients compared to

healthy controls, although studies conducting script-driven imagery failed to reveal

increased amygdala activity in PTSD subjects (Bremner, Narayan, et al., 1999;

Bremner, Staib, et al., 1999; Shin, et al., 1999). Furthermore, amygdala engagement

during the processing of fearful faces is a reliable and consistent finding in the fMRI

literature, whereas amygdala enhancement as reaction to angry or neutral faces has

been reported less consistently (Fusar-Poli, et al., 2009). The amygdala can

habituate during repeated exposure to emotional stimuli (Breiter, et al., 1996; Fischer,

et al., 2003; Schwartz, et al., 2003; Wright, et al., 2001). Time courses of left and

right amygdala activity (mean beta values within the left and right amygdala, data not

shown) did not reveal evidence of amygdala habituation during the whole

experimental period, neither in DID patients nor in controls. However, the amygdala

is not only restricted to signaling of fear, but is also involved in the evaluation of

salient (Sander, Grafman, & Zalla, 2003) and novel stimuli (Blackford, Buckholtz,

Avery, & Zald, 2010). It has been shown that the amygdala is activated most strongly

at the beginning of a stimulus series (Büchel, Morris, Dolan, & Friston, 1998). Hence,


41

the blockwise manner, in which our stimuli were presented, might explain the non

significant amygdala activity in our study. It could also be possible that the amygdala

of DID patients was consistently overactivated even before negative stimuli were

presented. This idea accords with results of other imaging studies showing that

anxious individuals have increased anticipatory activity in the amygdala preceding

stimuli with prior known negative, neutral, or ambiguous emotional valence (Brühl, et

al., 2011; Nitschke, et al., 2009).

Comparisons in which ANP’s brain activation was contrasted to other

conditions did not give significant results (i.e., DIDanp-DIDep, DIDanp-CONanp; see

Table 3 and 4). This finding indicates a relatively decreased BOLD signal all over the

brain for this type of dissociative part, suggesting low involvement in subliminally

presented faces.

There was increased activation in many a priori defined brain regions for EP in

DID patients compared to EP in controls, but fewer differences for ANP in DID

patients compared to EP in these patients. We therefore checked post hoc if these

differences also existed for ANP in DID patients compared to EP in controls (DIDanp-

CONep N-S, data not shown). We found enhanced activity in the dorsal brainstem,

lingual gyrus (with some voxels extending to the temporal occipital fusiform gyrus),

and motor-related areas such as the putamen and the (pre-)supplementary motor

area. While this pattern resembles the one for DIDep, it was less pronounced. It thus

seems that ANP’s decreased involvement in consciously perceived trauma-related

cues (Reinders, et al., 2003; Reinders, Nijenhuis, et al., 2006) has roots in ANP’s

subdued preconscious reactivity to trauma-related cues.

This study is the first to document that foremost as EP, DID patients

specifically focus on, and seem to be alarmed by preconsciously perceived neutral

faces. Consistent with the neural findings and our fourth hypothesis, EP in DID

patients also showed significantly slower RTs to neutral faces and a tendency to

slower RTs to angry faces compared to ANP in DID patients and EP in controls (see

Figure 7). This face- and dissociative part-specific effect could also be observed in

the direct comparison between RTs related to neutral and angry faces. This

comparison yielded a significantly longer RT in the neutral face condition in EP of

DID patients only (see Figure 8).


42

Emotionally neutral faces may be threatening to them for a variety of reasons.

First, it can be hard to disambiguate these expressions (“what does this face

mean?”), particularly following emotional neglect (“this person may not care about

me”) and abuse (“this person seems calm, but for how long, what emotion will he or

she show next?”). Consistent with this interpretation, patients with borderline

personality disorder (BPD) regarded neutral faces as threatening, and demonstrated

a hyperactivated amygdala when supraliminally confronted with these faces

(Donegan, et al., 2003). BPD, DID, and dissociative symptoms are all intimately

related to a context of unstable and disrupted interpersonal relationships (Benjamin,

1993; Dutra, et al., 2009; Kelley, et al., 2002; Korol, 2008; Linehan, 1993; Ogawa, et

al., 1997). As the type of dissociative part of the personality that is fixed in the

traumatic past, EP may regard neutral faces as untrustworthy and threatening, and

thus become hypervigilant when confronted with them, and prepare motor defensive

reactions. Neutral faces can also express affective unavailability (of caretakers), a

condition that all DID patients in the study reported (neglect and abuse by family

members). The quality of the early caregiving relationship is linked to dissociation in

that affective parental unavailability and disorganised attachment in childhood are

major predictors of dissociative symptoms in adulthood (Dutra, et al., 2009; Ogawa,

et al., 1997). Our results fit findings of grave effects of still faces on children

(Mesman, Van IJzendoorn, & Bakermans-Kranenburg, 2009; Tronick, Als, Adamson,

Wise, & Brazelton, 1978), particularly in individuals who are neglected, abused, and

insecurely attached. They generally add to the evidence for a pivotal role of

emotional neglect and emotional unavailability of caretakers in DID.

Our data contrast with the findings of Hermans et al. (2006), who reported

longer RTs to angry compared to neutral faces in EP of DID patients. This conflicting

finding might be related to several methodological differences between these studies

in relation to stimulation, such as the facial and masking stimuli, the design of the

subliminal presentation, and the presentation time. While our study presented facial

stimuli for 16.7 msec, Hermans et al. presented these stimuli for 25 msec. Cognitive

theories of anxiety maintain that the attentional bias toward threatening material

occurs at a preconscious level (Cisler & Koster, 2010). The stage of sensory

reactivity at which this bias emerges in DID has not been investigated systematically

to date. There is neurophysiological evidence showing that the signals transmitted by


43

neurons in the visual cortex increase as a function of stimulus length (Rolls, Tovee, &

Panzeri, 1999). In other words, the shorter the presentation time, the less sensory

signals for the discrimination of a face are provided. Neutral faces have an uncertain

emotional valence and, therefore, require deeper processing demands. It might be

speculated that the slightly shorter presentation time in our study particularly

increased preconscious fixation in EP on neutral facial expressions, as EP is focused

on threat or potential threat cues (Van der Hart, et al., 2006). Future studies are

needed to test this hypothesis.

Our fifth and last hypothesis was that the identified behavioral and neural

differences for ANP and EP in DID patients would not be matched by controls, who

were instructed and motivated to simulate ANP and EP. Controls showed a tendency

to inverse RTs and neural activation patterns for these different prototypical parts.

That is, as ANP, the actors tended to react like EP in DID patients, and as EP like

ANP in these patients. The actors were thus unable to simulate DID with respect to

behavioral and neural reactivity, which contradicts the sociocognitive model of DID.

Compared to EP, as ANP, controls had amygdala activity in the neutral face condition

(see Table 3), but neither brainstem activity nor a longer RT. Whereas the neutral

faces were thus salient (Davis & Whalen, 2001; LeDoux, 1998) for ANP-simulating

controls, they did not arouse them or attract much preconscious attention, as

happened for authentic EP. The current findings add to the psychobiological

evidence (Hermans, et al., 2006; Reinders, et al., 2012) that DID is neither an effect

of suggestion and fantasy, nor of role-playing.

The findings have strong implications for the clinical context in dealing with

DID patients and suggest that therapists of DID patients must be emotionally and

behaviorally engaged. Therapeutic neutrality will probably scare them, particularly as

EP, triggering and reinforcing conditioned emotional and defensive reactions. As EP,

these patients will tend to perceive an emotionally neutral therapist as an emotionally

unavailable caretaker. These effects may not be immediately visible when an ANP is

dominant due to ANP’s mental avoidance and under-engagement. However, ANP

and EP can be activated in parallel (Van der Hart, et al., 2006), so that the therapist’s

neutrality can nonetheless affect the patient as one or more EPs. This interpretation

is consistent with clinical observations (Van der Hart, et al., 2006). For example, ANP

may report that EP is negatively affected by the therapist’s neutrality. It may also


44

happen that ANP does not notice or report this emotionality in an EP, but that EP

responds in the described emotional sense in a later stage, while expressing that

she/he felt rejected, confused, or afraid when the therapist was emotionally

un(der)engaged.

This study has several limitations. Our sample size was relatively small. This

was due to the difficulty in finding DID patients who are able to alternate between

ANP and EP at request and to remain activated, particularly as EP, for a substantial

period of time in an fMRI environment. Patients who can perform this feat are the

ones who have been in treatment for at least several years. Because treatment of

DID fosters integration between the different dissociative parts and integration of

traumatic memories, studies such as ours are prone to underestimate naturally

existing biopsychosocial differences between these subsystems of the personality. In

order to check if the actors had understood and followed the instructions to simulate

an ANP and EP, patients and controls completed as ANP and EP the STAI-S (Laux,

et al., 1981) immediately after the fMRI measurement. Explorative data analysis

revealed that, in contrast to the behavioral and neural data, no inverse simulation

pattern could be observed (see Table 1). That is, as ANP, the actors tended to react

like ANP in DID patients, and as EP like EP in these patients. However, no significant

differences were observed between and within groups. Therefore, the STAI-S does

not seem to be an appropriate measurement to examine adherence to simulation

instructions. In future studies, other assessments such as self-report should be

included. DID patients have considerable comorbidity (Ellason, Ross, & Fuchs,

1996). Future studies will need to evaluate axis I and axis II comorbidity and address

covariations between this comorbidity and patterns of neural activation. Another

limitation of the study is that only two of our patients were free of medication.

Medication washout is not feasible with DID patients. However, medication does not

explain the observed differences between ANP and EP in DID patients.

In conclusion, the current study shows that two prototypical parts of the

personality in DID patients, ANP and EP, have different biopsychosocial reaction

patterns to backward masked neutral and angry faces that controls were unable to

simulate. Fixed in active defense, as EP, DID patients engage in early and automatic

scanning of facial expressions. Avoiding threat cues, as ANP, they are underinvolved


45

in the faces. These results and interpretations are consistent with clinical

observations and TSDP, but inconsistent with the sociocognitive model of DID.

5.1.6. Supplementary Findings

Supplementary Findings 1

Determination of awareness: subjective measurement

Participants were as ANP and EP invited to report what they saw on the screen

during the fMRI measurement. Apart from one EP, who reported seeing evil

grimaces, all dissociative parts of the personality only described the black-and-white

dotted mask and the colored dots. Because two EPs in a previous study (Hermans,

et al., 2006) also detected backward masked faces, it may be that some EPs are

extraordinary hypervigilant regarding potential threat cues, and therefore detect even

impressions of faces that for other individuals and for ANP remained below the level

of conscious awareness. Still, this EP’s hit rate for the objective measurement

described below (42.85%) was comparable to the mean hit rate of the patient group

(see Supplementary Table 1).

Determination of awareness: objective measurement

Following the fMRI measurement, patients (functioning as ANP) and controls were

subliminally presented 56 faces (14 stimuli per face condition) on the screen inside

the scanner room, using the same lighting conditions. After the subliminal

presentation of each face, we supraliminally projected this target face together with a

randomly chosen face matched in sex and emotional expression, and requested the

participants to say or guess which of these two faces had been previously projected

subliminally. Due to technical problems, one Presentation logfile of an actor was not

stored and could not be used for the statistical analysis. The mean hit rate for

patients as well as controls was approximately 50% (see Supplementary Table 1),

implying a level of detectability at chance level (Kihlstrom, et al., 1992). Hence, the

participants had not consciously seen the experimental faces.


46

Supplementary Findings 2

We examined the projector’s capacity, using a light sensor (Vishay Semiconductors),

to project pictures within the refresh rate of the computer’s graphic card (NVIDIA

Quadro FX 1700, 60-Hz). The sensor was fixed on the screen while the computer

was running a sequence of alternating black-and-white images with a presentation

time of 16.67 msec. The sensor’s output was measured by a digital oscilloscope

(APS 230). The actual presentation time of the projector was around 16.5 msec ± 2

msec. It thus projected the subliminal pictures within the critical time limit.

Supplementary Table 1. Objective determination of awareness (forced-choice task) in ANP

DID patients Controls

(n=15) (n=14)

Hits (%) 50.71±9.66 51.28±9.67

Note. DID, Dissociative identity disorder; mean percentage hit ± 1 SD is reported


47

5.2. Experiment 2: Resting-state paradigm

Dissociative part-dependent resting-state activity: A controlled fMRI perfusion

study of dissociative identity disorder

Submission to a peer-reviewed journal intended

Authors:

Yolanda R. Schlumpf, MSca, A. A. T. Simone Reinders, PhDb,c, Ellert R. S. Nijenhuis,

PhDd, Roger Luechinger, PhDe, Matthias J. P. Van Osch, PhDf, Lutz Jäncke, PhDa,g

a Division of Neuropsychology, Institute of Psychology, University of Zurich, Switzerland

b Department of Neuroscience, University Medical Center Groningen, and BCN Neuroimaging Center,

University of Groningen, Groningen, The Netherlands

c Department of Psychosis Studies, Institute of Psychiatry, King’s College London, London, United

Kingdom

d Top Referent Trauma Center Mental Health Care Drenthe, Assen, The Netherlands

e Institute for Biomedical Engineering, University and ETH Zurich, Switzerland

f Department of Radiology, C.J. Gorter Center for High-Field MRI, Leiden University Medical Center,

Leiden, The Netherlands

g International Normal Aging and Plasticity Imaging Center, University of Zurich, Switzerland

Keywords: dissociative identity disorder, arterial spin labeled perfusion, resting-

state, default mode activity, self-referential processing

Acknowledgments: This research was supported by the Forschungskredit of the

University of Zurich. A.A.T.Simone Reinders is supported by the Netherlands

Organization for Scientific Research (www.nwo.nl), NWO-VENI grant no. 451-07-009.

We would like to thank the colleagues of Prof. Jäncke’s lab for their helpful comments

and Franz Liem for his technical support. We are indebted to Ekaterina Weder and

Eva Zimmermann for their collaboration as research clinicians. Special thanks go to

the patients and their therapists for participating in the study.


48

5.2.1. Abstract

Background: In accordance with the Theory of Structural Dissociation of the

Personality (TSDP), studies of dissociative identity disorder (DID) have documented

that two prototypical dissociative subsystems of the personality, known as the

“Emotional Part” (EP) and the “Apparently Normal” Part (ANP), have different

psychobiological reactions to supraliminal and subliminal trauma-related cues. High

and low fantasy prone controls instructed and motivated to simulate ANP and EP in

DID had different neural and psychophysiological reactions.

Methods: Arterial spin labeling perfusion magnetic resonance imaging was used to

test the hypotheses that ANP and EP in DID have different perfusion patterns in

response to instructions to relax and lay immobile in a brain scanner, and that

perfusion is different in ANP and EP simulating actors.

Results: Perfusion (p<0.001, uncorrected for multiple comparisons) was dependent

on ANP and EP in DID patients. Compared to EP, ANP showed increased thalamus

activity, and compared to ANP, EP had increased perfusion in the dorsomedial

prefrontal cortex, primary somatosensory cortex, and several motor-related areas.

Perfusion patterns for the simulated ANP and EP were different. Fitting their reported

role-play strategies, the actors activated brain structures involved in visual mental

imagery and empathizing feelings.

Conclusion: DID involves ANP and EP dependent neural resting-state differences.

Compared to ANP, EP activated brain structures involved in self-referencing and

sensorimotor actions more. Controls motivated and instructed to simulate ANP and

EP had different perfusion patterns. The findings are consistent with TSDP and

inconsistent with the idea that DID is caused by suggestion, fantasy proneness, and

role-playing.


49

5.2.2. Introduction

Consistent clinical observations and retrospective findings indicate that dissociative

identity disorder (DID) (American Psychiatric Association, 1994) is intimately related

to severe traumatization including emotional neglect (Van der Hart, et al., 2006). This

conclusion is supported by the results of prospective longitudinal research of

dissociation (Diseth, 2006; Dutra, et al., 2009; Ogawa, et al., 1997). Whereas most

theories of DID include traumatization as one of the causal factors of the disorder, the

sociocognitive model of DID entails the idea that the disorder is caused by

suggestion, fantasy proneness, and role-playing (Lilienfeld, et al., 1999; Merskey,

1992; Piper & Merskey, 2004; Spanos, 1994). However, studies showing that DID

can be caused by these factors is lacking, and patients with DID are not particularly

fantasy prone (Reinders, et al., 2012). In addition, mentally healthy women

(Hermans, et al., 2006), high and low fantasy prone women (Reinders, et al., 2012),

and actors (Schlumpf, et al., 2013) who were motivated and instructed to simulate

two different prototypes of dissociative parts were unable to simulate the

psychophysiological and neural activation patterns of these dissociative parts in

women with DID.

Several studies have compared psychobiological reactions of different

dissociative parts in DID, but advances in the field critically depend on theoretical

predictions with respect to the kind of biopsychosocial differences that exist among

different types of dissociative subsystems or “parts“ of the personality as a whole

biopsychosocial system (Nijenhuis, et al., 2002). The Theory of Structural

Dissociation of the Personality (TSDP) offers such hypotheses (Nijenhuis & Den

Boer, 2009; Nijenhuis, et al., 2002; Van der Hart, et al., 2006). The two major

prototypes that TSDP distinguishes are metaphorically referred to as “Emotional

Parts” (EP) and “Apparently Normal Parts” (ANP) of the personality. As ANP, DID

patients aim to fulfill functions in daily life, and in this context they try to mentally and

behaviorally avoid traumatic memories and other trauma-related stimuli. ANP, thus,

has not or not sufficiently personified traumatic experiences and memories, can have

a degree of amnesia regarding the traumatic past, and is to some degree

depersonalized and bodily numbed. As EP, DID patients are fixated on traumatic

memories, that is, in nonintegrated sensorimotor and emotional reenactments of

traumatizing events. There are two major subtypes of EP (Nijenhuis & Den Boer,


50

2009). One subtype tends to engage in active mammalian defenses (e.g., freeze,

flight, attachment cry) and strong emotions, such as intense fear, in reaction to actual

or perceived threat. These reactions involve dominance of the sympathetic nervous

system. As this subtype, DID patients are generally self-conscious, emotional (e.g.,

fearful), body-oriented, and hyperaroused. The other subtype of EP predominantly

engages in passive mammalian defense (playing dead, tonic immobility) to actual or

perceived threat. This kind of defense would imply a degree of parasympathetically

mediated hypoarousal, emotional numbing, and bodily anesthesia.

TSDP is based on clinical and empirical evidence (Nijenhuis & Den Boer,

2009; Van der Hart, et al., 2006). For example, in a Positron Emission Tomography

(PET) study, DID patients listened as ANP and as EP to audiotaped descriptions of a

neutral autobiographical memory that these dissociative parts shared, as well as to a

description of a traumatic memory that was only autobiographical for EP (Reinders,

et al., 2003; Reinders, Nijenhuis, et al., 2006). ANP and EP (in Reinders, Nijenhuis,

et al. (2006) referred to as neutral identity state and trauma-related identity state,

respectively) had different psychophysiological and neural reaction patterns to the

trauma script. In line with TSDP, as ANP, the patients had a brain activation pattern

similar to patients with depersonalization disorder (Simeon, et al., 2000) and PTSD

patients with negative dissociative symptoms to trauma-related stimuli (Lanius, et al.,

2006; Lanius, et al., 2002). ANP had highly similar reaction patterns to the neutral

and the trauma script, which indicates a low emotional involvement in the trauma

script. As EP (subtype active defense), patients were deeply emotionally and bodily

engaged in this script. In contrast with ANP, EP had activation in many brain areas

also observed in PTSD patients who were confronted with a personalized trauma

script and who reacted with positive symptoms such as hyperarousal (Lanius, et al.,

2001; Rauch, et al., 1996; Shin, et al., 2001). As EP but not as ANP, DID patients

showed a significant increase in heart rate and blood pressure and a significant

decrease in heart rate variability in reaction to the trauma script. In sum, EP was

psychobiologically hyperaroused, and ANP was underengaged.

The same paradigm was repeated with healthy matched controls (Reinders, et

al., 2012). Neither high nor low fantasy prone, mentally healthy women instructed and

motivated to simulate ANP and EP had the psychophysiological and neural activation

patterns of the genuine ANP and EP in DID patients. This finding contradicts the


51

sociocognitive view of DID (Giesbrecht, et al., 2008; Lilienfeld, et al., 1999;

Merckelbach, Devilly, et al., 2002; Merckelbach & Muris, 2001; Merskey, 1992;

Spanos, 1994).

Using a conjunction analysis (Price & Friston, 1997; Price, Moore, & Friston,

1997), Reinders, Nijenhuis et al. (2006) demonstrated that ANP and EP were

associated with two different neural networks that are independent of the type of the

memory script they listened to. The authors suggested that these networks might be

involved in functioning as two different prototypes of dissociative parts. If this idea

holds, ANP and EP should have different neural characteristics when instructed to

rest, that is, to relax, close their eyes, and lay immobile on the back in the narrow

enclosed MRI space with their head fixed, and without the distraction of a more

specific task. According to TSDP, this assignment is emotionally challenging for DID

patients, as most of them have been chronically abused and emotionally neglected.

The situation would be particularly demanding for them as EP. The experimental

procedure could trigger trauma-related memories, in which EP is fixated, and that

ANP attempts to avoid.

The study of resting-state neural activity has recently become an important

area of neuroimaging. Of special interest is the so called default mode network

(DMN), a set of brain areas consisting of the medial prefrontal cortex (MPFC),

posterior cingulate (PCC) in addition to midline parietal structures, lateral parietal

regions, and medial and lateral temporal lobes (Gusnard & Raichle, 2001; Raichle, et

al., 2001; Raichle & Snyder, 2007). The DMN is activated in response to rest

instructions and is deactived during the execution of goal-directed tasks (Fox, et al.,

2005; Fransson, 2005; Greicius, Krasnow, Reiss, & Menon, 2003; Greicius & Menon,

2004; Mazoyer, et al., 2001; Shulman, et al., 1997; Tian, et al., 2007). Converging

evidence suggests that the DMN is critical for general self-referential processing,

such as autobiographical memory, self-reflection, self-awareness (i.e. introspection),

and stimulus-independent thought (Andrews-Hanna, et al., 2010; Buckner, et al.,

2008; Mason, et al., 2007; Northoff, et al., 2006).

The goals of the current study were to examine and compare brain perfusion

patterns for ANP and EP in DID patients and ANP and EP in simulating actors

following the rest instructions described above. Rest instructions do not imply that the

participants are actually resting. The term resting-state thus merely refers to the state


52

that rest instructions elicit. The comparison of patients and controls was to test the

idea that DID involves suggestion and role-playing rather than a trauma-related

condition (Merckelbach, Devilly, et al., 2002; Merskey, 1992).

To date, no study investigated so called resting-state perfusion differences in

ANP and EP in DID. A Single-Photon Emission Computed Tomography (SPECT)

study yielded bilateral orbitofrontal hypoperfusion and left lateral hyperperfusion

during rest for a type of dissociative part in DID described as the “host” compared to

healthy volunteers (Sar, et al., 2001). No significant perfusion differences were

observed between the host, defined as the dissociative part of the personality that is

most of the time present during a usual day (Putnam, 1997), and a different type of

dissociative part. We suspect that in most cases, the host was an ANP, but it is

unclear if the “alter” involved a second ANP, or an EP. Sar et al. (2001) may have

compared two ANP’s rather than an ANP and an EP. If so, this may explain why they

did not find different patterns of brain activity for the tested dissociative parts.

A different but not incompatible possibility is that SPECT is insufficiently

sensitive to measure perfusion differences in response to rest instructions. In the

current study, we used more sensitive arterial spin labeling (ASL), which generates

PET-like images without the need of a radioactive tracer. ASL provides a quantitative

CBF measurement, and is therefore particularly useful in the investigation of

individual differences in brain metabolism (Detre, et al., 2012).

Considerations based on TSDP and previous research findings lead us to

hypothesize that (i) there are perfusion differences for DID patients and simulating

controls. In particular, we predicted that (ia) compared to the controls, DID patients

show relative higher activation in areas which commonly exhibit increased neural

activity following rest instructions (default mode activity). Looking at the comparison

from the other side, we hypothesized that (ib) controls compared to DID patients elicit

a brain pattern distinct from the default mode activity because according to TSDP,

simulating an ANP and EP and being a genuine ANP and EP constitute different

mental states. We furthermore hypothesized that in response to the described rest

instructions, (ii) ANP and EP in DID have different patterns of brain perfusion and that

(iii) comparisons of ANP and EP simulating controls yield different neural reactivity

patterns than comparisons of ANP and EP in DID patients.


53

5.2.3. Methods

Participants

Fifteen female DID patients were included in the study. This sample was also used in

a study on the functional correlates of subliminally presented faces (Schlumpf, et al.,

2013). We enrolled Swiss and German patients, who were recruited from private

practitioners of psychiatry and psychotherapy and psychiatric outpatient

departments. All participants fulfilled the diagnostic criteria of DID according to DSM-

IV (American Psychiatric Association, 1994). For the sake of the study, the clinical

diagnoses were independently checked by experts in dissociative disorders using the

German version of the Structured Clinical Interview for DSM-IV Dissociative

Disorders (SCID-D) (Steinberg, 1993), the (SKID-D) (Gast, et al., 2000). The therapy

of the participating patients had to have progressed to a treatment phase involving

exposure to trauma-related memories (Steele, et al., 2005; Van der Hart, et al.,

2006). Individuals with any of the following conditions were excluded: comorbid

psychosis, drug abuse or addiction, antisocial or histrionic personality disorder, and a

neurological or organic brain disease. Thirteen patients were medicated at the time of

the measurement, predominantly with antidepressant medication. Two patients were

free of medication.

The control group consisted of fifteen female actors, who were motivated to

simulate ANP and EP. There were no significant differences between the control and

patient group in age (controls: M=43.2 years, SD=10.4; patients: M=43.3 years,

SD=9.1; t(28)=0.019, p>0.05) and educational level (controls: M=4.7, SD=1.2;

patients: M=4.1, SD=1.5; t(26.099)=-1.341, p>0.05; the educational level was

assessed by a 7-point Likert scale based on the common European educational

system). To ensure that none of the controls had a dissociative disorder, PTSD,

and/or major depression, the controls completed the German version of the

Posttraumatic Diagnostic Scale (PDS) (Ehlers, et al., 1996) and the Beck Depression

Inventory II (BDI-II) (Hautzinger, et al., 2006) and were interviewed by clinical experts

in dissociative disorders using the SKID-D (Gast, et al., 2000). The actors were

carefully informed about the characteristics of ANP and EP using written information

on TSDP (Van der Hart, et al., 2006). They also watched a video showing a DID

patient, who alternates between ANP and EP. The controls were instructed and


54

motivated to create an ANP and EP and were requested to practice simulating ANP

and EP as often as they deemed necessary to effectively simulate ANP and EP, but

at least three times before the MRI measurement. Each subject was informed about

risks and inconveniences associated with the experiment. All subjects gave written

informed consent. The local ethics committee (cantonal ethical commission of Zurich)

approved the study in compliance with the Helsinki Declaration.

Experimental design and procedure

The subjects were instructed to relax with their eyes closed and to stay motionless

during the functional magnetic resonance (fMRI) measurement. All participants were

first tested as ANP and next as EP, because starting with the less anxious

dissociative part might be less demanding for them. The switch between the different

dissociative parts of the personality took place outside the scanner, if needed with

minimal guidance from the research clinician. To check for inadvertent switches to a

different dissociative part than the intended ANP or EP, we asked the participants

after each run what part had been present during the measurement. One ANP and

two EP runs had to be repeated due to a switch to and/or a co-activation of an

unintended dissociative part.

Image acquisition and data preprocessing

All magnetic resonance imaging (MRI) data were obtained at the University Hospital

of Zurich with a 3-T Philips Achieva whole-body magnetic resonance imaging

equipped with an eight-channel Philips SENSE head coil. Resting regional cerebral

perfusion (rCBF) images were acquired with a pseudo-continuous ASL (p-CASL)

sequence with background suppression (saturation of the imaging slice preceding the

labeling and inversion pulses 1680 msec and 2760 msec after the saturation pulse)

and a single shot echo-planar imaging (EPI) readout (TR/TE=4180/12 msec, SENSE

factor 2.5). The duration of the labeling was 1650 msec and the image was acquired

after a delay of 1525 msec. The sequence consisted of 23 slices of 6mm slice

thickness acquired in ascending order with a 3x3mm2 in-plane resolution. During a

single run, 35 pairs of control/label image volumes were measured over a total scan


55

time of 5 minutes. An additional M0 image was acquired for measurement of the

magnetization of arterial blood (same sequence as ASL without labeling or

background suppression, TR=10s). A 3D MPRAGE T1-weighted anatomical scan

was acquired for anatomical reference and post-processing.

The data of three controls and one patient were excluded due to huge

movement artifacts and low signal quality. One patient reported to have fallen asleep

during the ANP and to have switched several times during the EP run. One patient

was not able to undergo the MRI measurement, and the data of one patient were lost

due to a storage failure at the MRI center. The final brain imaging statistical analysis

was performed with data of 11 participants in the patient group and 12 in the control

group.

Resting-state rCBF maps were calculated using in-house programmed

MATLAB scripts performing a simple pair-wise subtraction of control and label

images (Van Osch, et al., 2009). Further analyses were performed with the statistical

parametric mapping software SPM8 (http://www.fil.ion.ucl.ac.uk/spm). rCBF maps

were normalized to the EPI template (Wastling, et al., 2009), which transformed them

into MNI space (new voxel size=2x2x2mm3). The normalized rCBF maps were

spatially smoothed with an 8-mm full width at half-maximum (FWHM) Gaussian

kernel.

The preprocessed data were analyzed using a flexible factorial design that

consisted of two independent variables resulting in a 2×2 ANOVA with repeated

measures on the second factor: Group (two levels: DID/CON), Type of dissociative

part of the personality (two levels: ANP/EP). The second factor will be referred to as

Type in the rest of the article. In order to correct for biological variation in total CBF,

the mean gray matter (GM) CBF was included in the analysis as a covariate of no

interest. The mean GM signal per subject was calculated over a GM mask obtained

from the segmentation of the 3D T1 image by thresholding the GM probability images

at 0.5. Only the GM signal was taken into account, as a previous study revealed that

GM perfusion showed most variability between sessions (Gevers, et al., 2011).

The study design allows the calculation of various effects, i.e. main effect of

Group, main effect of Type, and an interaction effect of Group by Type. Our main

hypotheses were tested using one-sided t-tests. Group differences between the

patients (DID) and controls (CON) were assessed with two two-sample t-tests (DID-


56

CON, CON-DID) based on the mean perfusion map of ANP and EP of every single

participant. The participants were measured as ANP and EP in the patient group

(DIDanp/DIDep) and in the control group (CONanp/CONep). Four planned

comparisons consisting of Type effects between groups (DIDanp-CONanp, CONanp-

DIDanp; DIDep-CONep, CONep-DIDep) and four planned comparisons consisting of

Type effects within groups (DIDanp-DIDep, DIDep-DIDanp; CONanp-CONep,

CONep-CONanp) were performed. An explicit binary mask provided by FSL

(http://www.fmrib.ox.ac.uk/fsl) was applied at the level of the statistical interference to

remove extracranial voxels. The mask was normalized to MNI space and had the

same dimension and voxel size as the rCBF maps.

We accepted uncorrected significant levels (i.e., voxel level of significance

uncorrected [unc.] for multiple testing) of p<0.001 and a minimum cluster-size of 12

voxels due to the fact that the ASL signal has an inherently low signal to noise ratio

(SNR) (Detre, et al., 2012). Statistical thresholds of similar sizes were used in

previous resting-state perfusion (Schuff, et al., 2011) and BOLD (Yin, et al., 2011)

fMRI studies. Only the most significant finding of a brain area and first peak of a

cluster are reported in Table 6 to 9. The cluster locations were labeled using the

Harvard-Oxford cortical and subcortical structural atlases (Desikan, et al., 2006) and

by visual inspection on a high-resolution T1-weighted image in FSL. Subregions in

the cingulate cortex were named according to Vogt’s division based on

cytoarchitectonic characteristics (Vogt, 2005). The results are restricted to activations

in the GM, as white matter perfusion measurements are still challenging with ASL

(Van Osch, et al., 2009).


57

5.2.4. Results

Repeated measures ANOVA

Results for the main effects and interaction effect are listed in Table 6. Significant

rCBF differences for the Type main effect, independent of Group, and for the Group

main effect, independent of Type, were found. In addition, significant perfusion

differences were observed due to an interaction effect between Type and Group.

Table 6. Main effect of Group, main effect of Type (ANP/EP), and interaction effect on resting-state regional cerebral blood flow (rCBF)

Note. R/L, left or right hemisphere; kE, cluster-size in voxels (one voxel is 2x2x2mm); Pre-SMA, pre-supplementary motor area; DMPFC, dorsomedial prefrontal cortex a MNI coordinates (in mm) refer to the maximum of signal change in each region

Group differences

Group differences are given in Table 7. In line with our first hypothesis, we found

positive perfusion differences in the patient group compared to the control group

(DID-CON) and positive perfusion differences in the control group compared to the

patient group (CON-DID).

DID showed higher perfusion than CON in the temporal pole of the middle

temporal gyrus, in medial posterior and lateral inferior parietal regions (precuneus,

angular gyrus), and in the dorsomedial prefrontal cortex (DMPFC). In CON compared


58

to DID, we observed increased perfusion in the middle frontal gyrus and occipital

fusiform gyrus.

Table 7. Group differences in resting-state regional cerebral blood flow (rCBF)

Note. R/L, left or right hemisphere; kE, cluster-size in voxels (one voxel is 2x2x2mm); DID, patient group; CON, control group; DMPFC, dorsomedial prefrontal cortex a MNI coordinates (in mm) refer to the maximum of signal change in each region

Planned comparisons

Between-group comparisons of Type (i.e., two different types of dissociative parts of

the personality, ANP/EP) are listed in Table 8. Type comparisons within groups are

given in Table 9. We found significant rCBF differences in all eight planned

comparisons.

Between-group Type comparisons

Significant rCBF changes for both ANP and EP between the groups are in

accordance with our first hypothesis.

Compared to CONanp, DIDanp was associated with more activation in the

temporal pole of the middle temporal gyrus, in the lateral inferior and posterior medial

parietal lobe (angular gyrus, precuneus), and dorsal posterior cingulate cortex

(dPCC) (DIDanp-CONanp). In the inverse contrast (CONanp-DIDanp), we revealed a

higher perfusion in the middle frontal gyrus. An increased activation in the temporal

pole of the middle temporal gyrus, in the precuneus, and angular gyrus, found in the

contrast DIDanp-CONanp, could also be observed in DIDep compared to CONep

(DIDep-CONep). CONep compared to DIDep (CONep-DIDep) showed higher


59

activation in the right thalamus, middle frontal gyrus, hippocampus, occipital fusiform

gyrus, and lateral occipital cortex.

Within-group Type comparisons

The second hypothesis that DIDanp and DIDep differ in resting-state perfusion could

not been rejected, because we found significant rCBF differences in DIDanp-DIDep

and DIDep-DIDanp. In line with our third hypothesis, comparisons of CONanp and

CONep yielded different neural reactivity patterns than comparisons of DIDanp and

DIDep.

DIDanp had more perfusion in the bilateral thalamus than DIDep (DIDanp-

DIDep). In the inverse contrast (DIDep-DIDanp), we found increased perfusion in the

primary somatosensory cortex and in several motor-related brain areas including the

primary motor cortex and higher-order motor areas (pre-supplementary motor area

[pre-SMA], premotor cortex). In addition, DMPFC hyperperfusion could be observed

(Figure 10).

Figure 10. Significant rCBF increases in genuine EP (DIDep) compared to genuine ANP (DIDanp) in (A) the primary somatosensory cortex, primary motor cortex, premotor cortex and in (B) the pre-supplementary motor area (pre-SMA) and dorsomedial prefrontal cortex (DMPFC).

In CONanp compared to CONep (CONanp-CONep), we revealed higher brain

activation in the bilateral thalamus and in extrastriate regions of the occipital pole. In

the inverse contrast (CONep-CONanp), we observed a higher perfusion in insular-

opercular regions (anterior insula, frontal operculum) and in inferior frontal areas

(pars triangularis of the inferior frontal gyrus, orbitofrontal cortex [OFC]).


60

Table 8. Type (ANP/EP) effects between groups on resting-state regional cerebral blood flow (rCBF)

Note. R/L, left or right hemisphere; kE, cluster-size in voxels (one voxel is 2x2x2mm); DIDanp, ANP DID group; DIDep, EP DID group; CONanp, ANP control group; CONep, EP control group; dPCC, dorsal posterior cingulate cortex; DMPFC, dorsomedial prefrontal cortex a MNI coordinates (in mm) refer to the maximum of signal change in each region


61

Table 9. Type (ANP/EP) effects within groups on resting-state regional cerebral blood flow (rCBF)

Note. R/L, left or right hemisphere; kE, cluster-size in voxels (one voxel is 2x2x2mm); DIDanp, ANP DID group; DIDep, EP DID group; CONanp, ANP control group; CONep, EP control group; Pre-SMA, pre-supplementary motor area; DMPFC, dorsomedial prefrontal cortex; OFC, orbitofrontal cortex a MNI coordinates (in mm) refer to the maximum of signal change in each region


62

5.2.5. Discussion

This is the first fMRI perfusion study measuring brain perfusion in rest instructions in

DID patients. As hypothesized, we found differences between DID patients and DID

simulating actors, as well as between two different prototypes of dissociative parts of

the personality (ANP and EP) in DID patients.

Compared to controls, DID patients showed higher resting-state metabolism in

several areas belonging to the DMN (i.e, temporal pole of middle temporal gyrus,

precuneus, angular gyrus, and DMPFC) (Raichle & Snyder, 2007). The default mode

activity of DID is in line with our first hypothesis and suggests that DID patients were

more involved in attending to their self-states when instructed to rest than controls.

In the inverse contrast (CON-DID), we found more perfusion in the middle

frontal gyrus and in the occipital fusiform gyrus for the controls. Neural processes

associated with intended and motivated role-playing of ANP and EP were clearly

distinct from those correlated with being ANP and EP following rest instructions. The

DMN is also called the “task-negative” network (Fox, et al., 2005). Whereas it shows

attenuated levels of neural activity at rest and during self-referential processes

(Andrews-Hanna, et al., 2010; Buckner, et al., 2008; Gusnard & Raichle, 2001;

Mason, et al., 2007; Northoff, et al., 2006; Raichle, et al., 2001), this network exhibits

activity decreases across many goal-directed tasks (Fox, et al., 2005; Fransson,

2005; Greicius, et al., 2003; Greicius & Menon, 2004; Mazoyer, et al., 2001;

Shulman, et al., 1997; Tian, et al., 2007). Enacting ANP and EP involves a goal-

directed task, which can explain the relative lower default mode activity for controls

compared to DID patients.

The between-group Type effects fit these interpretations. Of special interest is

the increased activity in the precuneus, angular gyrus, and temporal pole of the

middle temporal gyrus for ANP and EP in DID patients when contrasted with the

corresponding simulated ANP and EP (i.e., DIDanp-CONanp, DIDep-CONep). These

areas are part of the DMN (Gusnard & Raichle, 2001). The precuneus is the area of

the brain with the highest resting-state perfusion and with perfusion decreases during

non-self-referential, goal-directed actions (Cavanna & Trimble, 2006). We therefore

conclude that in contrast to the DID-simulating controls, the DID patients engaged as

ANP and EP in self-referential actions following our relaxation instructions.


63

In line with our second hypothesis, we found different patterns of resting-state

perfusion for ANP and EP in the patients. Consistent with TSDP, they specifically

reported that not having a more explicit task to focus on while laying in the scanner

was threatening. Compared to EP, ANP showed more metabolism in the bilateral

thalamus (DIDanp-DIDep), and right thalamus activity was higher in controls

simulating EP than in authentic EP (CONep-DIDep). However, controls simulating

ANP also had more bilateral thalamus metabolism than controls simulating EP

(CONanp-CONep). Whereas relatively high thalamus activity for ANP in DID patients

may not be a DID-specific finding, our result parallels prior PTSD studies conducted

under rest (Kim, et al., 2007) or using script-driven symptom provocation paradigms

(Lanius, et al., 2005; Lanius, et al., 2001; Lanius, et al., 2003). Lanius et al. (2001,

2003, 2005) have reported that flashback/reliving PTSD patients (i.e., subjects

characterized with positive dissociative/EP-like symptoms) had relatively decreased

thalamic activation during the recall of traumatic memories, while “dissociated” PTSD

subjects (i.e., subjects characterized with negative dissociative/ ANP-like symptoms)

were associated with a relative increased thalamic activity. In the neurobiological

model of Krystal and colleagues, the thalamus plays a central role (Krystal, Bennett,

Bremner, Southwitck, & Charney, 1995). The idea is that sensory and arousal signals

parallel in the thalamus, the brain structure that relays the transmission of bodily

sensations to target brain areas, such as the prefrontal cortex and cingulate gyrus,

being involved in affect regulation, and amygdala and hippocampus. Under condition

of high arousal, this transmission is altered. Kim et al. (2007) found a positive

correlation between right thalamic blood flow following rest instructions and the

severity of current re-experiencing symptoms in PTSD patients (the more rCBF in the

right thalamus decreased, the less reliving symptoms occured). The authors

speculated that the lowering of thalamic activity represents a withdrawal of attention

from external sensory stimuli, which may provoke re-experiencing symptoms. It may

also be that EP becomes focused on interoceptive, bodily-emotional cues when they

feel threatened. Their perception of threat may involve classically conditioned stimuli

that tend to reactivate traumatic memories--in which EP are fixed, and implied high

arousal levels. Traumatic memories do not involve narratives, but are sensorimotor

and highly emotional.


64

In consert with these findings and hypotheses, our results suggest that as

ANP, DID patients are more open to external sensory stimuli than as an EP who is

prone to engage in active defense. This would particularly apply when they feel

threatened as this EP. Because of ANP’s habitual tendency to be numb and

depersonalized, they may not have been that alarmed by our instructions to relax,

close their eyes, and stay immobile in a loud narrow space. As EP, however, these

instructions and conditions may have reminded them of traumatizing circumstances.

To cope with the demanding situation, EP may have become focused on subjectively

threatening internal cues, implying low thalamus perfusion. At the same time, they

may have become self-aware, focused on internally alarming bodily and emotional

cues, and prone to reactivate painful memories.

Indeed, comparing EP to ANP in DID patients (DIDep-DIDanp), we found

increased rCBF in the primary somatosensory cortex, in several motor-related brain

areas, and in the DMPFC (see Figure 10). In a number of independent studies, self-

referential action was associated with activity in the DMPFC (Gusnard, Akbudak,

Shulman, & Raichle, 2001; Kjaer, Nowak, & Lou, 2002; Macrae, Moran, Heatherton,

Banfield, & Kelley, 2004). We suggest that in DID patients compared to ANP, EP was

attending more to his/her self-state and somatosensory sensations. The primary

motor cortex and the premotor cortex are involved in action planning and action

execution (Kawashima, Rolland, & O'Sullivan, 1994), and the pre-SMA in the

inhibition of motor responses (Neubert & Klein, 2010). Combining these findings, we

interpret that as EP, the patients were highly aware of being a body in a threatening

situation. This awareness might have triggered a tendency to engage in defense

motor reactions, which had to be inhibited in order to be able to fulfill the given

resting-state instructions.

In line with our third hypothesis, comparisons of ANP and EP in controls

yielded different neural reactivity patterns than comparisons of ANP and EP in DID

patients. The actors reported that they used two major strategies to fulfill their

simulation task: 1) imagining being another person and 2) trying to experience this

other person’s feelings. According to cognitive and social neuroscience, the first

strategy can be described as visual mental imagery (Kosslyn, Ganis, & Thompson,

2001) and the second as empathizing (Hein & Singer, 2008).


65

Visual imagery elicits neural activity in visual areas (Kosslyn, et al., 1993;

Kosslyn, et al., 2001). The increased perfusion in the occipital pole for controls

simulating ANP compared to controls enacting EP (CONanp-CONep) suggests that

as ANP, actors particularly engaged in visual imagery. As the participants were

requested to keep their eyes closed, activation in occipital areas cannot be explained

by visual perception.

The inverse contrast (CONep-CONanp) revealed a higher perfusion in the

anterior insula, pars triangularis of the inferior frontal gyrus, frontal operculum, and

OFC, which are known to be neural underpinnings of empathy. There are different

definitions of empathy in the literature. The second strategy for simulating ANP and

EP mentioned above involved empathy in the sense of “Einfühlen”, that is “feeling

into someone” (Barnes & Thagard, 1997; Eisenberg & Strayer, 1987). The anterior

anterior insula is associated with empathy for pain (Jackson, Meltzoff, & Decety,

2005; Singer, et al., 2004). Pain can occur beyond nociception and can be

generalized to mental suffering of any sort (Craig, 2003), such as laying in a scanner

as a traumatized anxious (part of a) person. The pars triangularis and the frontal

operculum are part of the mirror neuron system (MNS). The main function of the MNS

pertains to simulation. For example, observing another person’s actions increases

the firing rate of neurons that are also active when we actually perform those actions

ourselves (Gallese & Goldman, 1998). Thus, the MNS is involved in understanding

the actions and intentions of others (Blakemore & Decety, 2001; Rizzolatti &

Craighero, 2004). Neuroimaging studies in autism spectrum disorder patients

(Dapretto, et al., 2006) and healthy adults (Carr, Iacoboni, Dubeau, Mazziotta, &

Lenzi, 2003) also suggest that the MNS plays a pivotal role in empathy. Carr et al.

(2003) proposed that in concert with the anterior insula, the MNS is involved in

grasping the emotional states of others by physically and emotionally feeling what it

is like to engage in the observed action. The OFC has been found to be active in

empathy tasks as well (Decety & Meyer, 2008; Decety, Michalska, & Akitsuki, 2008;

Hynes, Baird, & Grafton, 2006). OFC functioning is critical for social cognition and

socially appropriate behavior. Taken together, our data support the idea that DID-

simulated controls engaged in envisioning and feeling of what one is not, that is, in

simulating ANP and EP.


66

The study has several limitations. First, although our sample is the largest

sample included in an fMRI study to date, it was still relatively small. This was due to

the difficulty finding DID patients who are able to alternate between ANP and EP at

request and to remain activated, particularly as EP, for a substantial period of time in

an fMRI environment. Second, patients who can perform this feat are the ones who

have been in treatment for at least several years. Because treatment of DID fosters

integration between the different dissociative parts and integration of traumatic

memories, studies such as ours are prone to underestimate biopsychosocial

differences between these subsystems of the personality in untreated individuals with

DID. Another limitation of the study is that only two of our patients were free of

medication. Medication washout is not feasible with DID patients. However, it is

important to note that medication does not explain the observed differences between

ANP and EP in DID.

In conclusion, the current study demonstrates for the first time that in contrast

to DID-simulating actors, particularly but not exclusively as EP, DID patients activated

brain structures known to be involved in attending self-states, as they responded to

relaxation and immobilization instructions in a challenging environment. The study

adds to the evidence from supraliminal and subliminal neuroimaging studies of ANP

and EP in DID (Hermans, et al., 2006; Reinders, et al., 2003; Reinders, Nijenhuis, et

al., 2006; Reinders, et al., 2012; Schlumpf, et al., 2013) that suggestion, role-playing,

and fantasy proneness do not explain the disorder. The present study is also the first

to show that the examined different prototypes of dissociative parts are associated

with different patterns of brain activity when given rest instructions. The findings are

consistent with clinical observations and TSDP, but inconsistent with the

sociocognitive model of DID.

General discussion

67

6. General discussion

6.1. Summary of the results and embedding in the theoretical background

In the following, the most important results of Experiment 1 and Experiment 2 are

summarized and embedded in the theoretical background.

6.1.1. Experiment 1

Experiment 1 revealed that as EP, DID patients engage in preconscious perception

of angry and neutral faces. Enhanced activity in the brainstem and motor-related

areas and the longest RTs in the neutral face condition indicate that EP was aroused

by (Jones, 2003) and particularly fixated (Bakvis, et al., 2009; Putman, et al., 2004;

Van Honk, et al., 1998, 2000) on neutral faces. EP may regard neutral faces as

untrustworthy and threatening, become hypervigilant when confronted with them, and

prepare motor defensive reactions. EP is continuously scanning the environment for

potential threats, and neutral faces do not express a clear emotion and are therefore

not easy to disambiguate. This might be a reason why in EP neutral faces have

attracted much preconscious attention. Another explanation is based on findings

showing that emotional neglect in childhood is a major predictor of dissociative

symptoms in adulthood (Dutra, et al., 2009; Ogawa, et al., 1997). In this context,

neutral faces might become an aversively conditioned stimulus for EP, as these faces

remind of parental affective unavailability.

In contrast, as ANP, DID patients showed a relative depressed BOLD signal

all over the brain in response to subliminally presented angry and neutral faces,

suggesting less involvement in these faces. It thus seems that ANP’s decreased

engagement in consciously perceived trauma-related cues (Reinders, et al., 2003;

Reinders, Nijenhuis, et al., 2006) has roots in this dissociative part’s reduced

preconscious reactivity to trauma-related cues.

Actors were not able to simulate the neural and behavioral reactions observed

for ANP and EP in DID. The results of the experiment have major clinical implications

in that they show how the disorder can be maintained over decades. EP is the holder

of the trauma memory and, therefore, a trauma-related stimulus for ANP. Trauma

memories involve aversive sensorimotor and highly emotional experiences that relate

General discussion

68

to the traumatic events (Brewin, 2001; Van der Kolk, 1997). In terms of classical

conditioning, when ANP is intruded by EP, ANP is exposed to a cluster of

unconditioned stimuli, which subsequently can become conditioned fear stimuli. In

this context, EP can become a conditioned stimulus for reminders of the terrible

events possibly causing ANP to consciously and, in line with our research idea,

preconsciously mentally avoid EP. On the other hand, if EP is aware of this rejection,

EP may become phobic of the neglectful or rejecting ANP, as neglect is a common

precursor of DID (Dutra, et al., 2009; Lyons-Ruth, et al., 2006; Ogawa, et al., 1997).

Consequently, EP will tend to fear and avoid ANP as well. The development of a

unilateral or bilateral conditioned fear and phobic reactions to each other precludes

posttraumatic integration of traumatic memories as well as the integration of ANP and

EP (Van der Hart, et al., 2006).

The results also offer suggestions for psychotherapy of trauma-related

dissociative disorders. That is, they propose that ANP and EP must be exposed to

each other to enhance integration. Furthermore, the clinical findings suggest that

therapists of DID patients must be emotionally and behaviorally engaged in order not

to trigger and reinforce conditioned emotional and defensive reactions. Therapeutic

neutrality will probably scare the patients, particularly as EP, as they may tend to

perceive an emotionally neutral therapist as an emotionally unavailable caretaker.

6.1.2. Experiment 2

Previous studies (Hermans, et al., 2006; Reinders, et al., 2003; Reinders, Nijenhuis,

et al., 2006) provide insights into dissociative part-dependent reactions to trauma-

related stimuli. Experiment 2 extends these findings to a task-free condition. For a

DID patient, to relax and lay immobile in a loud narrow brain scanner is, particularly

as EP, a challenging and threatening setting. Thus, rest instructions do not imply that

DID patients are actually resting. They rather try to deal with the situation of being a

self in a threatening situation. The experiment allowed investigation of ANP’s and

EP’s habitual tendencies to deal with threat in a task-free condition. Our data suggest

that compared to ANP, as EP, DID patients are self-conscious, body-oriented, and

focused in active defense. Furthermore, our data parallel findings demonstrating that

the thalamus plays a crucial role in regulating dissociative states (Kim, et al., 2007;

Lanius, et al., 2005; Lanius, et al., 2001; Lanius, et al., 2003). Reduced thalamus

General discussion

69

activity seems to be related to positive dissociative symptoms (i.e., EP-like

symptoms), whereas enhanced thalamic activity is associated with negative

dissociative symptoms (i.e., ANP-like symptoms).

The results of the current experiment have not only the potential to increase

the understanding of the psychobiology of DID. We also demonstrated that being a

genuine DID patient and simulating DID patient are incompatible at the level of neural

activity. DID patients followed our rest instructions and elicited a perfusion pattern

that is routinely active during rest (default mode activity). In contrast, the actors’

perfusion pattern indicates that they engaged in the role-playing task by envisioning

(Kosslyn, et al., 2001) being a dissociative part of a DID patient and empathizing

his/her feelings (Hein & Singer, 2008).

6.2. Conclusion

In conclusion, the findings of the present dissertation suggest that in DID patients,

neural and behavioral reactions in response to masked faces and brain perfusion in a

task-free condition are dependent on the type of dissociative part that is dominant

during the measurement. Both experiments also demonstrate that actors instructed

and motivated to simulate ANP and EP are not able to mimic the neuronal patterns of

genuine DID patients. This finding is of major clinical importance because it adds to

the evidence that DID is an authentic disorder and cannot be explained by role-

playing. The results and interpretations are consistent with clinical observations and

the TSDP (Van der Hart, et al., 2006), but contradict the sociocognitive view of DID.

6.3. Implications and directions for future studies

The major aims of the presented experiments were successfully achieved, and the

findings give rise to new research questions.

Experiment 1 indicated that trauma leads to alterations in the very early face

processing stream. The experiment should be repeated using electro-

encephalography (EEG) to benefit from the high temporal resolution in the recording

of electrical activity (Jäncke, 2005). In addition, psychophysiological variables, such

as heart rate, heart rate variability, and skin conductance, should be assessed.

General discussion

70

These peripheral measurements are a useful compliment to fMRI data and help to

interpret patterns of arousal and emotionality more concisely.

There are indications that alterations in the default mode network connectivity

(i.e. temporal correlation between brain regions) are strongly associated with the

pathophysiology of mental disorders (Van den Heuvel & Hulshoff Pol; Whitfield-

Gabrieli & Ford, 2012). A functional connectivity analysis is needed to answer the

question of whether the functionality of the DMN and its role in self-referential

processes is disturbed in DID patients. Additionally, a non-simulating healthy control

group should be measured with the same ASL sequence in order to further

investigate neural resting-state patterns of DID patients compared to healthy controls

and to overcome the paradoxical situation of simulating resting DID patients

characterizing the actors.

71

References Aguirre, G. K., Detre, J. A., Zarahn, E., & Alsop, D. C. (2002). Experimental design

and the relative sensitivity of BOLD and perfusion fMRI. Neuroimage, 15(3), 488-500.

Akyuz, G., Dogan, O., Sar, V., Yargic, L. I., & Tutkun, H. (1999). Frequency of dissociative identity disorder in the general population in Turkey. Compr Psychiatry, 40(2), 151-159.

Amaral, D. G., Price, J. L., Pitkanen, A., & Carmichael, S. T. (1992). Anatomical organization of primate amygdaloid complex. In W. Aggleton (Ed.), The Amygdala: Neurobiological Aspects of Emotion, Memory and Mental Dysfunction (pp. 1-66). New York: Wiley-Liss.

American Psychiatric Association (1994). Diagnostic and Statistical Manual of Mental Disorders DSM-IV (4th ed.). Washington, DC: American Psychiatric Association.

Andreasen, N. C., O'Leary, D. S., Cizadlo, T., Arndt, S., Rezai, K., Watkins, G. L., et al. (1995). Remembering the past: two facets of episodic memory explored with positron emission tomography. Am J Psychiat, 152, 1576-1585.

Andrews-Hanna, J. R., Reidler, J. S., Huang, C., & Buckner, R. L. (2010). Evidence for the default network's role in spontaneous cognition. J Neurophysiol, 104(1), 322-335.

Armony, J. L., Corbo, V., Clement, M. H., & Brunet, A. (2005). Amygdala response in patients with acute PTSD to masked and unmasked emotional facial expressions. Am J Psychiatry, 162(10), 1961-1963.

Ashburner, J., & Friston, K. J. (2005). Unified segmentation. Neuroimage, 26(3), 839-851.

Bakvis, P., Roelofs, K., Kuyk, J., Edelbroek, P. M., Swinkels, W. A., & Spinhoven, P. (2009). Trauma, stress, and preconscious threat processing in patients with psychogenic nonepileptic seizures. Epilepsia, 50(5), 1001-1011.

Barnes, A., & Thagard, P. (1997). Empathy and analogy. Dialogue Can Philos Rev, 36 705–720.

Baumgartner, T., Willi, M., & Jancke, L. (2007). Modulation of corticospinal activity by strong emotions evoked by pictures and classical music: a transcranial magnetic stimulation study. Neuroreport, 18(3), 261-265.

Benjamin, L. S. (1993). Interpersonal Diagnosis and Treatment of Personality Disorders (2 ed.). New York: Guilford.

Bishop, S. J. (2007). Neurocognitive mechanisms of anxiety: an integrative account. Trends Cogn Sci, 11(7), 307-316.

Blackford, J. U., Buckholtz, J. W., Avery, S. N., & Zald, D. H. (2010). A unique role for the human amygdala in novelty detection. Neuroimage, 50(3), 1188-1193.

Blakemore, S. J., & Decety, J. (2001). From the perception of action to the understanding of intention. Nat Rev Neurosci, 2(8), 561-567.

Breiter, H. C., Etcoff, N. L., Whalen, P. J., Kennedy, W. A., Rauch, S. L., Buckner, R. L., et al. (1996). Response and habituation of the human amygdala during visual processing of facial expression. Neuron, 17(5), 875-887.

Bremner, J. D., Narayan, M., Staib, L. H., Southwick, S. M., McGlashan, T., & Charney, D. S. (1999). Neural correlates of memories of childhood sexual

72

abuse in women with and without posttraumatic stress disorder. Am J Psychiatry, 156(11), 1787-1795.

Bremner, J. D., Staib, L. H., Kaloupek, D., Southwick, S. M., Soufer, R., & Charney, D. S. (1999). Neural correlates of exposure to traumatic pictures and sound in Vietnam combat veterans with and without posttraumatic stress disorder: a positron emission tomography study. Biol Psychiatry, 45(7), 806-816.

Brewin, C. R. (2001). A cognitive neuroscience account of posttraumatic stress disorder and its treatment. Behav Res Ther, 39(4), 373-393.

Brühl, A. B., Rufer, M., Delsignore, A., Kaffenberger, T., Jancke, L., & Herwig, U. (2011). Neural correlates of altered general emotion processing in social anxiety disorder. Brain Res, 1378, 72-83.

Bryant, R. A., Kemp, A. H., Felmingham, K. L., Liddell, B., Olivieri, G., Peduto, A., et al. (2008). Enhanced amygdala and medial prefrontal activation during nonconscious processing of fear in posttraumatic stress disorder: an fMRI study. Hum Brain Mapp, 29(5), 517-523.

Büchel, C., Morris, J., Dolan, R. J., & Friston, K. J. (1998). Brain systems mediating aversive conditioning: an event-related fMRI study. Neuron, 20(5), 947-957.

Buckner, R. L., Andrews-Hanna, J. R., & Schacter, D. L. (2008). The brain's default network: anatomy, function, and relevance to disease. Ann N Y Acad Sci, 1124, 1-38.

Buxton, R. B. (2002). Introducing to Functional Magnetic Resonance Imaging. Cambridge, UK: Cambridge University Press.

Carr, L., Iacoboni, M., Dubeau, M. C., Mazziotta, J. C., & Lenzi, G. L. (2003). Neural mechanisms of empathy in humans: a relay from neural systems for imitation to limbic areas. Proc Natl Acad Sci U S A, 100(9), 5497-5502.

Cavanna, A. E., & Trimble, M. R. (2006). The precuneus: a review of its functional anatomy and behavioural correlates. Brain, 129(Pt 3), 564-583.

Cheesman, J., & Merikle, P. M. (1984). Priming with and without awareness. Percept Psychophys, 36, 387-395.

Christoff, K., Gordon, A. M., Smallwood, J., Smith, R., & Schooler, J. W. (2009). Experience sampling during fMRI reveals default network and executive system contributions to mind wandering. Proc Natl Acad Sci U S A, 106(21), 8719-8724.

Cisler, J. M., & Koster, E. H. (2010). Mechanisms of attentional biases towards threat in anxiety disorders: An integrative review. Clin Psychol Rev, 30(2), 203-216.

Coons, P. M., Milstein, V., & Marley, C. (1982). EEG studies of two multiple personalities and a control. Arch Gen Psychiatry, 39(7), 823-825.

Craig, A. D. (2003). Pain mechanisms: labeled lines versus convergence in central processing. Annu Rev Neurosci, 26, 1-30.

D'Esposito, M., Deouell, L. Y., & Gazzaley, A. (2003). Alterations in the BOLD fMRI signal with ageing and disease: a challenge for neuroimaging. Nat Rev Neurosci, 4(11), 863-872.

Dalenberg, C. J., Brand, B. L., Gleaves, D. H., Dorahy, M. J., Loewenstein, R. J., Cardena, E., et al. (2012). Evaluation of the evidence for the trauma and fantasy models of dissociation. Psychol Bull, 138(3), 550-588.

Dapretto, M., Davies, M. S., Pfeifer, J. H., Scott, A. A., Sigman, M., Bookheimer, S. Y., et al. (2006). Understanding emotions in others: mirror neuron dysfunction in children with autism spectrum disorders. Nat Neurosci, 9(1), 28-30.

73

Davis, M., & Whalen, P. J. (2001). The amygdala: vigilance and emotion. Mol Psychiatry, 6(1), 13-34.

Decety, J., & Meyer, M. (2008). From emotion resonance to empathic understanding: a social developmental neuroscience account. Dev Psychopathol, 20(4), 1053-1080.

Decety, J., Michalska, K. J., & Akitsuki, Y. (2008). Who caused the pain? An fMRI investigation of empathy and intentionality in children. Neuropsychologia, 46(11), 2607-2614.

Dell, P. F. (2006). A new model of dissociative identity disorder. Psychiatr Clin North Am, 29(1), 1-26, vii.

Dell, P. F., & O'Neil, J. A. (2009). Prefrace. In P. F. Dell & J. A. O'Neil (Eds.), Dissociation and the Dissociative Disorders: DSM-V and Beyond (pp. xix-xxi). New York: Routledge.

Desikan, R. S., Segonne, F., Fischl, B., Quinn, B. T., Dickerson, B. C., Blacker, D., et al. (2006). An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest. Neuroimage, 31(3), 968-980.

Detre, J. A., Rao, H., Wang, D. J., Chen, Y. F., & Wang, Z. (2012). Applications of arterial spin labeled MRI in the brain. J Magn Reson Imaging, 35(5), 1026-1037.

Detre, J. A., Zhang, W., Roberts, D. A., Silva, A. C., Williams, D. S., Grandis, D. J., et al. (1994). Tissue specific perfusion imaging using arterial spin labeling. NMR Biomed, 7(1-2), 75-82.

Diseth, T. H. (2006). Dissociation following traumatic medical treatment procedures in childhood: a longitudinal follow-up. Dev Psychopathol, 18(1), 233-251.

Donegan, N. H., Sanislow, C. A., Blumberg, H. P., Fulbright, R. K., Lacadie, C., Skudlarski, P., et al. (2003). Amygdala hyperreactivity in borderline personality disorder: implications for emotional dysregulation. Biol Psychiatry, 54(11), 1284-1293.

Dutra, L., Bureau, J. F., Holmes, B., Lyubchik, A., & Lyons-Ruth, K. (2009). Quality of early care and childhood trauma: a prospective study of developmental pathways to dissociation. J Nerv Ment Dis, 197(6), 383-390.

Ehlers, A., Steil, R., Winter, H., & Foa, E. B. (1996). Deutsche Übersetzung der Posttraumatic Diagnostic Scale (PDS). Oxford: University, Warneford Hospital.

Eisenberg, N., & Strayer, J. (1987). Critical issues in the study of empathy. In N. Eisenberg & J. Strayer (Eds.), Empathy and its Development (pp. 3-13). New York: Cambridge University Press.

Ellason, J. W., Ross, C. A., & Fuchs, D. L. (1996). Lifetime axis I and II comorbidity and childhood trauma history in dissociative identity disorder. Psychiatry, 59(3), 255-266.

Eysenck, M. W., Mogg, K., May, J., Richards, A., & Mathews, A. (1991). Bias in interpretation of ambiguous sentences related to threat in anxiety. J Abnorm Psychol, 100(2), 144-150.

Felmingham, K., Kemp, A. H., Williams, L., Falconer, E., Olivieri, G., Peduto, A., et al. (2008). Dissociative responses to conscious and non-conscious fear impact underlying brain function in post-traumatic stress disorder. Psychol Med, 38(12), 1771-1780.

Fink, G. R., Markowitsch, H. J., Reinkemeier, M., Bruckbauer, T., Kessler, J., & Heiss, W. D. (1996). Cerebral representation of one's own past: neural

74

networks involved in autobiographical memory. J Neurosci, 16(13), 4275-4282.

Fischer, H., Wright, C. I., Whalen, P. J., McInerney, S. C., Shin, L. M., & Rauch, S. L. (2003). Brain habituation during repeated exposure to fearful and neutral faces: a functional MRI study. Brain Res Bull, 59(5), 387-392.

Foote, B., Smolin, Y., Kaplan, M., Legatt, M. E., & Lipschitz, D. (2006). Prevalence of dissociative disorders in psychiatric outpatients. Am J Psychiatry, 163(4), 623-629.

Fox, M. D., Snyder, A. Z., Vincent, J. L., Corbetta, M., Van Essen, D. C., & Raichle, M. E. (2005). The human brain is intrinsically organized into dynamic, anticorrelated functional networks. Proc Natl Acad Sci U S A, 102(27), 9673-9678.

Fox, P. T., & Raichle, M. E. (1986). Focal physiological uncoupling of cerebral blood flow and oxidative metabolism during somatosensory stimulation in human subjects. Proc Natl Acad Sci U S A, 83(4), 1140-1144.

Fransson, P. (2005). Spontaneous low-frequency BOLD signal fluctuations: an fMRI investigation of the resting-state default mode of brain function hypothesis. Hum Brain Mapp, 26(1), 15-29.

Friedl, M. C., & Draijer, N. (2000). Dissociative disorders in Dutch psychiatric inpatients. Am J Psychiatry, 157(6), 1012-1013.

Friston, K. J., Holmes, A., Poline, J. B., Price, C. J., & Frith, C. D. (1996). Detecting activations in PET and fMRI: levels of inference and power. Neuroimage, 4(3 Pt 1), 223-235.

Friston, K. J., Worsley, K. J., Frackowiak, R. S. J., Mazziotta, J. C., & Evans, A. C. (1994). Assessing the significance of focal activations using their spatial extent. Hum Brain Mapp, 1, 210-220.

Fusar-Poli, P., Placentino, A., Carletti, F., Landi, P., Allen, P., Surguladze, S., et al. (2009). Functional atlas of emotional faces processing: a voxel-based meta-analysis of 105 functional magnetic resonance imaging studies. J Psychiatry Neurosci, 34(6), 418-432.

Galbraith, P. M., & Neubauer, P. J. (2000). Underwriting considerations for dissociative disorders. J Insur Med, 32(2), 71-78.

Gallese, V., & Goldman, A. (1998). Mirror neurons and the simulation theory of mind-reading. Trends Cogn Sci, 2(12), 493-501.

Gast, U., Hofmann, A., Oswald, T., & Zündorf, F. (2000). Das Strukturierte Klinische Interview für DSM-IV Dissoziative Störungen (SKID-D). Deutsche Fassung. Manual und Interviewheft. Göttingen: Hogrefe.

Gast, U., Rodewald, F., Nickel, V., & Emrich, H. M. (2001). Prevalence of dissociative disorders among psychiatric inpatients in a German university clinic. J Nerv Ment Dis, 189(4), 249-257.

Gevers, S., Van Osch, M. J., Bokkers, R. P., Kies, D. A., Teeuwisse, W. M., Majoie, C. B., et al. (2011). Intra- and multicenter reproducibility of pulsed, continuous and pseudo-continuous arterial spin labeling methods for measuring cerebral perfusion. J Cereb Blood Flow Metab, 31(8), 1706-1715.

Giesbrecht, T., Lynn, S. J., Lilienfeld, S. O., & Merckelbach, H. (2008). Cognitive processes in dissociation: An analysis of core theoretical assumptions. Psychol Bull, 134, 617-647.

Gleaves, D. H. (1996). The sociocognitive model of dissociative identity disorder: a reexamination of the evidence. Psychol Bull, 120(1), 42-59.

75

Gorno-Tempini, M. L., Pradelli, S., Serafini, M., Pagnoni, G., Baraldi, P., Porro, C., et al. (2001). Explicit and incidental facial expression processing: an fMRI study. Neuroimage, 14(2), 465-473.

Greenwald, A. G., Draine, S. C., & Abrams, R. L. (1996). Semantic activation without conscious identification in dichotic listening, parafoveal vision, and visual masking: A survey and appraisal. Science, 273, 1699-1702.

Greicius, M. D., Krasnow, B., Reiss, A. L., & Menon, V. (2003). Functional connectivity in the resting brain: a network analysis of the default mode hypothesis. Proc Natl Acad Sci U S A, 100(1), 253-258.

Greicius, M. D., & Menon, V. (2004). Default-mode activity during a passive sensory task: uncoupled from deactivation but impacting activation. J Cogn Neurosci, 16(9), 1484-1492.

Grillon, C., Lissek, S., Rabin, S., McDowell, D., Dvir, S., & Pine, D. S. (2008). Increased anxiety during anticipation of unpredictable but not predictable aversive stimuli as a psychophysiologic marker of panic disorder. Am J Psychiatry, 165(7), 898-904.

Gusnard, D. A., Akbudak, E., Shulman, G. L., & Raichle, M. E. (2001). Medial prefrontal cortex and self-referential mental activity: relation to a default mode of brain function. Proc Natl Acad Sci U S A, 98(7), 4259-4264.

Gusnard, D. A., & Raichle, M. E. (2001). Searching for a baseline: functional imaging and the resting human brain. Nat Rev Neurosci, 2(10), 685-694.

Hajcak, G., Molnar, C., George, M. S., Bolger, K., Koola, J., & Nahas, Z. (2007). Emotion facilitates action: a transcranial magnetic stimulation study of motor cortex excitability during picture viewing. Psychophysiology, 44(1), 91-97.

Hautzinger, M., Keller, F., & Kühner, C. (2006). Beck Depressions-Inventar (BDI-II). Revision. Frankfurt a. M.: Harcourt Test Services.

Haxby, J. V., Hoffman, E. A., & Gobbini, M. I. (2000). The distributed human neural system for face perception. Trends Cogn Sci, 4(6), 223-233.

Hein, G., & Singer, T. (2008). I feel how you feel but not always: the empathic brain and its modulation. Curr Opin Neurobiol, 18(2), 153-158.

Hendler, T., Rotshtein, P., Yeshurun, Y., Weizmann, T., Kahn, I., Ben-Bashat, D., et al. (2003). Sensing the invisible: differential sensitivity of visual cortex and amygdala to traumatic context. Neuroimage, 19(3), 587-600.

Henke, K., Landis, T., & Markowitsch, H. J. (1994). Subliminal perception of words and faces. Int J Neurosci, 75(3-4), 181-187.

Henke, K., Mondadori, C. R., Treyer, V., Nitsch, R. M., Buck, A., & Hock, C. (2003). Nonconscious formation and reactivation of semantic associations by way of the medial temporal lobe. Neuropsychologia, 41(8), 863-876.

Henke, K., Treyer, V., Nagy, E. T., Kneifel, S., Dursteler, M., Nitsch, R. M., et al. (2003). Active hippocampus during nonconscious memories. Conscious Cogn, 12(1), 31-48.

Hermans, E. J., Nijenhuis, E. R., Van Honk, J., Huntjens, R. J., & Van der Hart, O. (2006). Identity state-dependent attentional bias for facial threat in dissociative identity disorder. Psychiatry Res, 141(2), 233-236.

Holaway, R. M., Heimberg, R. G., & Coles, M. E. (2006). A comparison of intolerance of uncertainty in analogue obsessive-compulsive disorder and generalized anxiety disorder. J Anxiety Disord, 20(2), 158-174.

76

Holender, D. (1986). Semantic activation without conscious identification in dichotic listening, parafoveal vision, and visual masking: A survey and appraisal. Behav Brain Sci, 9, 1-23.

Hughes, J. R., Kuhlman, D. T., Fichtner, C. G., & Gruenfeld, M. J. (1990). Brain mapping in a case of multiple personality. Clin Electroencephalogr, 21(4), 200-209.

Hynes, C. A., Baird, A. A., & Grafton, S. T. (2006). Differential role of the orbital frontal lobe in emotional versus cognitive perspective-taking. Neuropsychologia, 44(3), 374-383.

ISSD (1997). Guidlines for Treating Dissociative Identity Disorder (Multiple Personality) in Adults. Chicago: Author.

Jackson, P. L., Meltzoff, A. N., & Decety, J. (2005). How do we perceive the pain of others? A window into the neural processes involved in empathy. Neuroimage, 24(3), 771-779.

Jäncke, L. (2005). Methoden der Bildgebung in der Psychologie und den kognitiven Neurowissenschaften. Stuttgart: Kohlhammer.

Johnson, J. G., Cohen, P., Kasen, S., & Brook, J. S. (2006). Dissociative disorders among adults in the community, impaired functioning, and axis I and II comorbidity. J Psychiatr Res, 40(2), 131-140.

Jones, B. E. (2003). Arousal systems. Front Biosci, 8, s438-451. Kawashima, R., Rolland, P. E., & O'Sullivan, B. T. (1994). Fields in human motor

areas involved in preparation for reaching, actual reaching, and visumotor learning: A positron emission tomography study. J Neurosci, 14(6), 3462-3474.

Kelley, W. M., Macrae, C. N., Wyland, C. L., Caglar, S., Inati, S., & Heatherton, T. F. (2002). Finding the self? An event-related fMRI study. J Cogn Neurosci, 14(5), 785-794.

Kihlstrom, J. F., Barnhardt, T. M., & Tataryn, D. J. (1992). Implicit perception. In R. F. Bornstein & T. S. Pittman (Eds.), Perception Without Awareness: Cognitive, Clinical, and Social Perspectives (pp. 17-54). New York: Guilford Press.

Kim, S. J., Lyoo, I. K., Lee, Y. S., Kim, J., Sim, M. E., Bae, S. J., et al. (2007). Decreased cerebral blood flow of thalamus in PTSD patients as a strategy to reduce re-experience symptoms. Acta Psychiatr Scand, 116(2), 145-153.

Kjaer, T. W., Nowak, M., & Lou, H. C. (2002). Reflective self-awareness and conscious states: PET evidence for a common midline parietofrontal core. Neuroimage, 17(2), 1080-1086.

Korol, S. (2008). Familial and social support as protective factors against the development of dissociative identity disorder. J Trauma Dissociation, 9(2), 249-267.

Kosslyn, S. M., Alpert, N. M., Thomson, W. L., Maljkovic, V., Weise, S. B., Chabris, C. F., et al. (1993). Visual mental imagery activates topographically organized visual cortex: PET investigations. J Cogn Neurosci, 5, 635-642.

Kosslyn, S. M., Ganis, G., & Thompson, W. L. (2001). Neural foundations of imagery. Nat Rev Neurosci, 2(9), 635-642.

Krystal, J. H., Bennett, A. L., Bremner, J. D., Southwitck, S. M., & Charney, D. S. (1995). Toward a cognitive neuroscience of dissociation and altered memory functions in posttraumatic stress disorder. In F. M. J., D. S. Charney & A. Y. Deutsch (Eds.), Neurobiological and Clinical Consequences of Stress: From Normal Adaptions to PTSD (pp. 239-268). New York: Raven Press.

77

Lanius, R. A., Bluhm, R., Lanius, U., & Pain, C. (2006). A review of neuroimaging studies in PTSD: heterogeneity of response to symptom provocation. J Psychiatr Res, 40(8), 709-729.

Lanius, R. A., Williamson, P. C., Bluhm, R. L., Densmore, M., Boksman, K., Neufeld, R. W., et al. (2005). Functional connectivity of dissociative responses in posttraumatic stress disorder: a functional magnetic resonance imaging investigation. Biol Psychiatry, 57(8), 873-884.

Lanius, R. A., Williamson, P. C., Boksman, K., Densmore, M., Gupta, M., Neufeld, R. W., et al. (2002). Brain activation during script-driven imagery induced dissociative responses in PTSD: a functional magnetic resonance imaging investigation. Biol Psychiatry, 52(4), 305-311.

Lanius, R. A., Williamson, P. C., Densmore, M., Boksman, K., Gupta, M. A., Neufeld, R. W., et al. (2001). Neural correlates of traumatic memories in posttraumatic stress disorder: a functional MRI investigation. Am J Psychiatry, 158(11), 1920-1922.

Lanius, R. A., Williamson, P. C., Hopper, J., Densmore, M., Boksman, K., Gupta, M. A., et al. (2003). Recall of emotional states in posttraumatic stress disorder: an fMRI investigation. Biol Psychiatry, 53(3), 204-210.

Laux, L., Glanzmann, P., Schaffner, P., & Spielberger, C. D. (1981). Das State-Trait-Angstinventar. Theoretische Grundlagen und Handanweisung. Weinheim: Beltz Test GmbH.

LeDoux, J. E. (1998). The Emotional Brain: The Mysterious Underpinnings of Emotional Life. New York: Touchstone.

Lewis, D. O., Yeager, C. A., Swica, Y., Pincus, J. H., & Lewis, M. (1997). Objective documentation of child abuse and dissociation in 12 murderers with dissociative identity disorder. Am J Psychiatry, 154(12), 1703-1710.

Lilienfeld, S. O., Lynn, S. J., Kirsch, I., Chaves, J. F., Sarbin, T. R., Ganaway, G. K., et al. (1999). Dissociative identity disorder and the sociocognitive model: recalling the lessons of the past. Psychol Bull, 125(5), 507-523.

Linehan, M. M. (1993). Cognitive-behavioral Treatment of Borderline Personality Disorder. New York, N.Y.: Guilford Press.

Liu, T. T., & Brown, G. G. (2007). Measurement of cerebral perfusion with arterial spin labeling: Part 1. Methods. J Int Neuropsychol Soc, 13(3), 517-525.

Loftus, E. F., Coan, J., & Pickrell, J. E. (1996). Manufacturing false memories using bits of reality. In L. Reder (Ed.), Implicit Memory and Metacognition. Hillsdale, NJ: Lawrence Erlbaum Associates, Inc.

Loftus, E. F., & Ketcham, K. (1994). The Myth of Repressed Memory. New York: St. Martin's Press.

Loftus, E. F., & Pickrell, J. E. (1995). The formation of false memories. Psychiat Ann, 25, 720-725.

Logothetis, N. K., Pauls, J., Augath, M., Trinath, T., & Oeltermann, A. (2001). Neurophysiological investigation of the basis of the fMRI signal. Nature, 412(6843), 150-157.

Lundquist, D., Flykt, A., & Öhman, A. (1998). The Karolinska Directed Emotional Faces - KDEF, CD ROM from Department of Clinical Neuroscience, Psychology section, Karolinska Institute, ISBN 91-630-7164-9.

Lynn, S. J., Lilienfeld, S. O., Merckelbach, H., Giesbrecht, T., & Van der Kloet, D. (2012). Dissociation and dissociative disorders: challenging conventional wisdom. Curr Dir Psychol Sci, 21(48), 48-53.

78

Lyons-Ruth, K., Dutra, L., Schuder, M., & Bianchi, I. (2006). From infant attachment disorganization to adult dissociation: Relational adaptations or traumatic experiences? In R. Chevetz (Ed.), Dissociative Disorders (Vol. 29, pp. 63-86). Psychiatric Clinics of North America.

Macrae, C. N., Moran, J. M., Heatherton, T. F., Banfield, J. F., & Kelley, W. M. (2004). Medial prefrontal activity predicts memory for self. Cereb Cortex, 14(6), 647-654.

Malonek, D., & Grinvald, A. (1996). Interactions between electrical activity and cortical microcirculation revealed by imaging spectroscopy: implications for functional brain mapping. Science, 272(5261), 551-554.

Mason, M. F., Norton, M. I., Van Horn, J. D., Wegner, D. M., Grafton, S. T., & Macrae, C. N. (2007). Wandering minds: the default network and stimulus-independent thought. Science, 315(5810), 393-395.

Mazoyer, B., Zago, L., Mellet, E., Bricogne, S., Etard, O., Houde, O., et al. (2001). Cortical networks for working memory and executive functions sustain the conscious resting state in man. Brain Res Bull, 54(3), 287-298.

Merckelbach, H., à Campo, J., Hardy, S., & Giesbrecht, T. (2005). Dissociation and fantasy proneness in psychiatric patients: a preliminary study. Compr Psychiatry, 46(3), 181-185.

Merckelbach, H., Devilly, G. J., & Rassin, E. (2002). Alters in dissociative identity disorder. Metaphors or genuine entities? Clin Psychol Rev, 22(4), 481-497.

Merckelbach, H., Horselenberg, R., & Schmidt, H. (2002). Modeling the connection between self-reported trauma and dissociation in a student sample. Pers Indiv Differ, 32, 695-705.

Merckelbach, H., & Muris, P. (2001). The causal link between self-reported trauma and dissociation: a critical review. Behav Res Ther, 39(3), 245-254.

Merckelbach, H., Muris, P., Rassin, E., & Horselenberg, R. (2000). Dissociative experiences and interrogative suggestibility in college students. Pers Indiv Differ, 29, 1133-1140.

Merckelbach, H., Rassin, E., & Muris, P. (2000). Dissociation, schizotypy, and fantasy proneness in undergraduate students. J Nerv Ment Dis, 188(7), 428-431.

Merskey, H. (1992). The manufacture of personalities. The production of multiple personality disorder. Br J Psychiatry, 160, 327-340.

Mesman, J., Van IJzendoorn, M. H., & Bakermans-Kranenburg, M. J. (2009). The many faces of the Still-Face Paradigm: A review and meta-analysis. Dev Rev, 29, 120-162.

Metzinger, T. (2003). Being No One: The Self-Model Theory of Subjectivity. Cambridge, MA: MIT Press.

Morris, J. S., Ohman, A., & Dolan, R. J. (1998). Conscious and unconscious emotional learning in the human amygdala. Nature, 393(6684), 467-470.

Nakamura, K., Kawashima, R., Sato, N., Nakamura, A., Sugiura, M., Kato, T., et al. (2000). Functional delineation of the human occipito-temporal areas related to face and scene processing. A PET study. Brain, 123 ( Pt 9), 1903-1912.

Neubert, F. X., & Klein, M. C. (2010). What is driving inhibition-related activity in the frontal lobe? J Neurosci, 30(14), 4830-4832.

Nijenhuis, E. R., & Van der Hart, O. (2011). Dissociation in trauma: a new definition and comparison with previous formulations. J Trauma Dissociation, 12(4), 416-445.

79

Nijenhuis, E. R. S. (2004). Somatoform Dissociation: Phenomena, Measurement, and Theoretical Issues. New York: Norton.

Nijenhuis, E. R. S., & Den Boer, J. A. (2009). Psychobiology of traumatisation and trauma-related structural dissociation of the personality. In P. F. Dell & J. A. O’Neil (Eds.), Dissociation and the Dissociative Disorders: DSM-V and Beyond (pp. 337-367). New York: Routledge.

Nijenhuis, E. R. S., Van der Hart, O., & Steele, K. (2002). The emerging psychobiology of trauma-related dissociation and dissociative disorders. In H. D’Haenen, J. A. Den Boer & P. Willner (Eds.), Biological Psychiatry (pp. 1079-1098). London: Wiley.

Nijenhuis, E. R. S., Van der Hart, O., & Steele, K. (2004). Strukturelle Dissoziation der Persönlichkeitsstruktur, traumatischer Ursprung, phobische Residuen. In L. Reddemann, A. Hofmann & U. Gast (Eds.), Psychotherapie der dissoziativen Störungen (pp. 47-69). Stuttgart: Thieme.

Nitschke, J. B., Sarinopoulos, I., Oathes, D. J., Johnstone, T., Whalen, P. J., Davidson, R. J., et al. (2009). Anticipatory activation in the amygdala and anterior cingulate in generalized anxiety disorder and prediction of treatment response. Am J Psychiatry, 166(3), 302-310.

Northoff, G., Heinzel, A., de Greck, M., Bermpohl, F., Dobrowolny, H., & Panksepp, J. (2006). Self-referential processing in our brain--a meta-analysis of imaging studies on the self. Neuroimage, 31(1), 440-457.

Ogawa, J. R., Sroufe, L. A., Weinfield, N. S., Carlson, E. A., & Egeland, B. (1997). Development and the fragmented self: longitudinal study of dissociative symptomatology in a nonclinical sample. Dev Psychopathol, 9(4), 855-879.

Ogawa, S., Lee, T. M., Kay, A. R., & Tank, D. W. (1990). Brain magnetic resonance imaging with contrast dependent on blood oxygenation. Proc Natl Acad Sci U S A, 87(24), 9868-9872.

Ogawa, S., Menon, R. S., Tank, D. W., Kim, S. G., Merkle, H., Ellermann, J. M., et al. (1993). Functional brain mapping by blood oxygenation level-dependent contrast magnetic resonance imaging. A comparison of signal characteristics with a biophysical model. Biophys J, 64(3), 803-812.

Öhman, A. (2002). Automaticity and the amygdala: Nonconscious response to emotional faces. Curr Dir Psychol Sci, 11, 62-66.

Öhman, A. (2005). The role of the amygdala in human fear: automatic detection of threat. Psychoneuroendocrinology, 30(10), 953-958.

Öhman, A., & Soares, J. J. (1994). "Unconscious anxiety": phobic responses to masked stimuli. J Abnorm Psychol, 103(2), 231-240.

Oliveri, M., Babiloni, C., Filippi, M. M., Caltagirone, C., Babiloni, F., Cicinelli, P., et al. (2003). Influence of the supplementary motor area on primary motor cortex excitability during movements triggered by neutral or emotionally unpleasant visual cues. Exp Brain Res, 149(2), 214-221.

Osuch, E. A., Benson, B., Geraci, M., Podell, D., Herscovitch, P., McCann, U. D., et al. (2001). Regional cerebral blood flow correlated with flashback intensity in patients with posttraumatic stress disorder. Biol Psychiatry, 50(4), 246-253.

Pauling, L., & Coryell, C. D. (1936). The Magnetic Properties and Structure of the Hemochromogens and Related Substances. Proc Natl Acad Sci U S A, 22(3), 159-163.

80

Phan, K. L., Wager, T., Taylor, S. F., & Liberzon, I. (2002). Functional neuroanatomy of emotion: a meta-analysis of emotion activation studies in PET and fMRI. Neuroimage, 16(2), 331-348.

Phelps, E. A., O'Connor, K. J., Gatenby, J. C., Gore, J. C., Grillon, C., & Davis, M. (2001). Activation of the left amygdala to a cognitive representation of fear. Nat Neurosci, 4(4), 437-441.

Piper, A., & Merskey, H. (2004). The persistence of folly: A critical examination of dissociative identity disorder. Part I. The excesses of an improbable concept. Canadian Journal of Psychiatry, 49, 592-600.

Pitcher, D., Walsh, V., Yovel, G., & Duchaine, B. (2007). TMS evidence for the involvement of the right occipital face area in early face processing. Curr Biol, 17(18), 1568-1573.

Price, C. J., & Friston, K. J. (1997). Cognitive conjunction: a new approach to brain activation experiments. Neuroimage, 5(4 Pt 1), 261-270.

Price, C. J., Moore, C. J., & Friston, K. J. (1997). Subtractions, conjunctions, and interactions in experimental design of activation studies. Hum Brain Mapp, 5(4), 264-272.

Putman, P., Hermans, E., & Van Honk, J. (2004). Emotional stroop performance for masked angry faces: it's BAS, not BIS. Emotion, 4(3), 305-311.

Putnam, F. W. (1997). Dissociation in Children and Adolescents: A Developmental Perspective. New York: Guilford Press.

Raichle, M. E., MacLeod, A. M., Snyder, A. Z., Powers, W. J., Gusnard, D. A., & Shulman, G. L. (2001). A default mode of brain function. Proc Natl Acad Sci U S A, 98(2), 676-682.

Raichle, M. E., & Snyder, A. Z. (2007). A default mode of brain function: a brief history of an evolving idea. Neuroimage, 37(4), 1083-1090; discussion 1097-1089.

Rainer, G., Augath, M., Trinath, T., & Logothetis, N. K. (2001). Nonmonotonic noise tuning of BOLD fMRI signal to natural images in the visual cortex of the anesthetized monkey. Curr Biol, 11(11), 846-854.

Rauch, S. L., Van der Kolk, B. A., Fisler, R. E., Alpert, N. M., Orr, S. P., Savage, C. R., et al. (1996). A symptom provocation study of posttraumatic stress disorder using positron emission tomography and script-driven imagery. Arch Gen Psychiatry, 53(5), 380-387.

Rauch, S. L., Whalen, P. J., Shin, L. M., McInerney, S. C., Macklin, M. L., Lasko, N. B., et al. (2000). Exaggerated amygdala response to masked facial stimuli in posttraumatic stress disorder: a functional MRI study. Biol Psychiatry, 47(9), 769-776.

Reinders, A. A. T. S., Den Boer, J. A., & Buchel, C. (2005). The robustness of perception. Eur J Neurosci, 22(2), 524-530.

Reinders, A. A. T. S., Glascher, J., De Jong, J. R., Willemsen, A. T., Den Boer, J. A., & Buchel, C. (2006). Detecting fearful and neutral faces: BOLD latency differences in amygdala-hippocampal junction. Neuroimage, 33(2), 805-814.

Reinders, A. A. T. S., Nijenhuis, E. R. S., Paans, A. M., Korf, J., Willemsen, A. T., & Den Boer, J. A. (2003). One brain, two selves. Neuroimage, 20(4), 2119-2125.

Reinders, A. A. T. S., Nijenhuis, E. R. S., Quak, J., Korf, J., Haaksma, J., Paans, A. M., et al. (2006). Psychobiological characteristics of dissociative identity disorder: a symptom provocation study. Biol Psychiatry, 60(7), 730-740.

81

Reinders, A. A. T. S., Willemsen, A. T. M., Vos, H. P. J., Den Boer, J. A., & Nijenhuis, E. R. S. (2012). Fact or factitious? A psychobiological study of authentic and simulated dissociative identity states. PLoS One, 6(7), e39279.

Rifkin, A., Ghisalbert, D., Dimatou, S., Jin, C., & Sethi, M. (1998). Dissociative identity disorder in psychiatric inpatients. Am J Psychiatry, 155(6), 844-845.

Rizzolatti, G., & Craighero, L. (2004). The mirror-neuron system. Annu Rev Neurosci, 27, 169-192.

Rolls, E. T., Tovee, M. J., & Panzeri, S. (1999). The neurophysiology of backward visual masking: information analysis. J Cogn Neurosci, 11(3), 300-311.

Sakamoto, H., Fukuda, R., Okuaki, T., Rogers, M., Kasai, K., Machida, T., et al. (2005). Parahippocampal activation evoked by masked traumatic images in posttraumatic stress disorder: a functional MRI study. Neuroimage, 26(3), 813-821.

Sander, D., Grafman, J., & Zalla, T. (2003). The human amygdala: an evolved system for relevance detection. Rev Neurosci, 14(4), 303-316.

Sar, V., Akyuz, G., & Dogan, O. (2007). Prevalence of dissociative disorders among women in the general population. Psychiatry Res, 149(1-3), 169-176.

Sar, V., Unal, S. N., Kiziltan, E., Kundakci, T., & Ozturk, E. (2001). HMPAO SPECT study of regional cerebral blood flow in dissociative identity disorder. J Trauma Dissociation, 2(2), 5-25.

Schlumpf, Y. R., Nijenhuis, E. R. S., Chalavi, S., Weder, E. V., Zimmermann, E., Lüchinger, R., et al. (2013). Dissociative part-dependent biopsychosocial reactions to backward masked angry and neutral faces: An fMRI study of dissociative identity disorder. Neuroimage: Clinical, 3, 54-64.

Schuff, N., Zhang, Y., Zhan, W., Lenoci, M., Ching, C., Boreta, L., et al. (2011). Patterns of altered cortical perfusion and diminished subcortical integrity in posttraumatic stress disorder: an MRI study. Neuroimage, 54 Suppl 1, S62-68.

Schwartz, C. E., Wright, C. I., Shin, L. M., Kagan, J., Whalen, P. J., McMullin, K. G., et al. (2003). Differential amygdalar response to novel versus newly familiar neutral faces: a functional MRI probe developed for studying inhibited temperament. Biol Psychiatry, 53(10), 854-862.

Shin, L. M., Kosslyn, S. M., McNally, R. J., Alpert, N. M., Thompson, W. L., Rauch, S. L., et al. (1997). Visual imagery and perception in posttraumatic stress disorder. A positron emission tomographic investigation. Arch Gen Psychiatry, 54(3), 233-241.

Shin, L. M., McNally, R. J., Kosslyn, S. M., Thompson, W. L., Rauch, S. L., Alpert, N. M., et al. (1999). Regional cerebral blood flow during script-driven imagery in childhood sexual abuse-related PTSD: A PET investigation. Am J Psychiatry, 156(4), 575-584.

Shin, L. M., Orr, S. P., Carson, M. A., Rauch, S. L., Macklin, M. L., Lasko, N. B., et al. (2004). Regional cerebral blood flow in the amygdala and medial prefrontal cortex during traumatic imagery in male and female Vietnam veterans with PTSD. Arch Gen Psychiatry, 61(2), 168-176.

Shin, L. M., Whalen, P. J., Pitman, R. K., Bush, G., Macklin, M. L., Lasko, N. B., et al. (2001). An fMRI study of anterior cingulate function in posttraumatic stress disorder. Biol Psychiatry, 50(12), 932-942.

Shulman, G. L., Fiez, J. A., Corbetta, M., Buckner, R. L., Miezin, F. M., Raichle, M. E., et al. (1997). Common blood flow changes across visual tasks: II. Decreases in cerebral cortex. J Cogn Neurosci, 9, 648-663.

82

Simeon, D., Guralnik, O., Hazlett, E. A., Spiegel-Cohen, J., Hollander, E., & Buchsbaum, M. S. (2000). Feeling unreal: a PET study of depersonalization disorder. Am J Psychiatry, 157(11), 1782-1788.

Singer, T., Seymour, B., O'Doherty, J., Kaube, H., Dolan, R. J., & Frith, C. D. (2004). Empathy for pain involves the affective but not sensory components of pain. Science, 303(5661), 1157-1162.

Spanos, N. P. (1994). Multiple identity enactments and multiple personality disorder: A sociocognitive perspective. Psychol Bull, 116(1), 143-165.

Spanos, N. P. (1996). Multiple Identities and False Memories: A Sociocognitive Perspective. Washington, D.C.: American Psychological Association.

Steele, K., Van der Hart, O., & Nijenhuis, E. R. (2005). Phase-oriented treatment of structural dissociation in complex traumatization: overcoming trauma-related phobias. J Trauma Dissociation, 6(3), 11-53.

Steinberg, M. (1993). Structured Clinical Interview for DSM-IV Dissociative Disorders (SCID-D). Washington, DC: American Psychiatric Press.

Svoboda, E., McKinnon, M. C., & Levine, B. (2006). The functional neuroanatomy of autobiographical memory: a meta-analysis. Neuropsychologia, 44(12), 2189-2208.

Thulborn, K. R., Waterton, J. C., Matthews, P. M., & Radda, G. K. (1982). Oxygenation dependence of the transverse relaxation time of water protons in whole blood at high field. Biochim Biophys Acta, 714(2), 265-270.

Tian, L., Jiang, T., Liu, Y., Yu, C., Wang, K., Zhou, Y., et al. (2007). The relationship within and between the extrinsic and intrinsic systems indicated by resting state correlational patterns of sensory cortices. Neuroimage, 36(3), 684-690.

Tjandra, T., Brooks, J. C., Figueiredo, P., Wise, R., Matthews, P. M., & Tracey, I. (2005). Quantitative assessment of the reproducibility of functional activation measured with BOLD and MR perfusion imaging: implications for clinical trial design. Neuroimage, 27(2), 393-401.

Trickett, P. K., Noll, J. G., & Putnam, F. W. (2011). The impact of sexual abuse on female development: lessons from a multigenerational, longitudinal research study. Dev Psychophathol, 23, 453–476

Tronick, E., Als, H., Adamson, L., Wise, S., & Brazelton, T. B. (1978). The infant's response to entrapment between contradictory messages in face-to-face interaction. J Am Acad Child Psychiatry, 17(1), 1-13.

Tulving, E., Kapur, S., Craik, F. I., Moscovitch, M., & Houle, S. (1994). Hemispheric encoding/retrieval asymmetry in episodic memory: positron emission tomography findings. Proc Natl Acad Sci U S A, 91(6), 2016-2020.

Tutkun, H., Sar, V., Yargic, L. I., Ozpulat, T., Yanik, M., & Kiziltan, E. (1998). Frequency of dissociative disorders among psychiatric inpatients in a Turkish University Clinic. Am J Psychiatry, 155(6), 800-805.

Van Balen, L. (2005). Activation and localization of the emotional circuits in the brain: an fMRI study in patients with schizophrenia and healthy volunteers. Unpublished Master thesis, Rijksuniversiteit Groningen, Groningen.

Van den Heuvel, M. P., & Hulshoff Pol, H. E. (2010). Exploring the brain network: a review on resting-state fMRI functional connectivity. Eur Neuropsychopharmacol, 20(8), 519-534.

Van der Hart, O., Nijenhuis, E. R. S., & Steele, K. (2006). The Haunted Self: Structural Dissociation and the Treatment of Chronic Traumatization. New York: W.W. Norton & Company.

83

Van der Kolk, B. A. (1997). The psychobiology of posttraumatic stress disorder. J Clin Psychiatry, 58 Suppl 9, 16-24.

Van Honk, J., Tuiten, A., Van den Hout, M., Koppeschaar, H., Thijssen, J., De Haan, E., et al. (1998). Baseline salivary cortisol levels and preconscious selective attention for threat. A pilot study. Psychoneuroendocrinology, 23(7), 741-747.

Van Honk, J., Tuiten, A., Van den Hout, M., Koppeschaar, H., Thijssen, J., De Haan, E., et al. (2000). Conscious and preconscious selective attention to social threat: different neuroendocrine response patterns. Psychoneuroendocrinology, 25(6), 577-591.

Van Osch, M. J., Teeuwisse, W. M., Van Walderveen, M. A., Hendrikse, J., Kies, D. A., & Van Buchem, M. A. (2009). Can arterial spin labeling detect white matter perfusion signal? Magn Reson Med, 62(1), 165-173.

Van Zijl, P. C., Hua, J., & Lu, H. (2012). The BOLD post-stimulus undershoot, one of the most debated issues in fMRI. Neuroimage, 62(2), 1092-1102.

Vogt, B. A. (2005). Pain and emotion interactions in subregions of the cingulate gyrus. Nat Rev Neurosci, 6(7), 533-544.

Vuilleumier, P. (2005). How brains beware: neural mechanisms of emotional attention. Trends Cogn Sci, 9(12), 585-594.

Vuilleumier, P., & Pourtois, G. (2007). Distributed and interactive brain mechanisms during emotion face perception: evidence from functional neuroimaging. Neuropsychologia, 45(1), 174-194.

Wang, J., Aguirre, G. K., Kimberg, D. Y., Roc, A. C., Li, L., & Detre, J. A. (2003). Arterial spin labeling perfusion fMRI with very low task frequency. Magn Reson Med, 49(5), 796-802.

Wastling, S. J., O'Daly, O., Zelaya, F. O., Howard, M., Alsop, D. C., & O'Gorman, R. L. (2009). Quantitative comparison of methods for spatial normalisation of CASL perfusion MR images. Proc Intl Soc Mag Reson Med, 17.

Whalen, P. J., Rauch, S. L., Etcoff, N. L., McInerney, S. C., Lee, M. B., & Jenike, M. A. (1998). Masked presentations of emotional facial expressions modulate amygdala activity without explicit knowledge. J Neurosci, 18(1), 411-418.

Whitfield-Gabrieli, S., & Ford, J. M. (2012). Default mode network activity and connectivity in psychopathology. Annu Rev Clin Psychol, 8, 49-76.

Wiens, S., & Öhman, A. (2002). Unawareness is more than a chance event: comment on Lovibond and Shanks (2002). J Exp Psychol Anim Behav Process, 28(1), 27-31.

Wolf, R. L., & Detre, J. A. (2007). Clinical neuroimaging using arterial spin-labeled perfusion magnetic resonance imaging. Neurotherapeutics, 4(3), 346-359.

Wong, E. C. (1999). Potential and pitfalls of arterial spin labeling based perfusion imaging techniques for MRI. In C. T. W. Moonen & P. A. Bandettini (Eds.), Functional MRI (pp. 63-69). Heidelberg: Springer.

Wright, C. I., Fischer, H., Whalen, P. J., McInerney, S. C., Shin, L. M., & Rauch, S. L. (2001). Differential prefrontal cortex and amygdala habituation to repeatedly presented emotional stimuli. Neuroreport, 12(2), 379-383.

Yin, Y., Li, L., Jin, C., Hu, X., Duan, L., Eyler, L. T., et al. (2011). Abnormal baseline brain activity in posttraumatic stress disorder: a resting-state functional magnetic resonance imaging study. Neurosci Lett, 498(3), 185-189.

Zarahn, E., Aguirre, G. K., & D'Esposito, M. (1997). Empirical analyses of BOLD fMRI statistics. I. Spatially unsmoothed data collected under null-hypothesis conditions. Neuroimage, 5(3), 179-197.

84

Curriculum vitae

PERSONAL DATA Name Yolanda Schlumpf Date of Birth 30.01.1979 Place of Origin Mexico City Nationality Swiss EDUCATION 07/2009 – 09/2012 University of Zurich, Switzerland Institute of Psychology Division of Neuropsychology

PhD project: The Brain in Dissociative Identity Disorder: Reactions to Subliminal Facial Stimuli and a Task-Free Condition

International PhD program in neuroscience (Neuroscience Center Zurich)

01/2012 – 12/2012 University of Zurich, Switzerland Institute of Psychology

Member of the Peer Mentoring Group „Psycho-physiology“

11/2007 – 10/2009 University of Zurich, Switzerland

Master of Advanced Studies in Neuropsychology (Prof. Dr. Jäncke) 10/1999 – 12/2004 University of Zurich, Switzerland Institute of Psychology

Master of Science (Psychology, Psychopathology, Religious Science) EMPLOYMENT HISTORY 04/2008 – 03/2009 Psychiatric University Hospital Zurich, Switzerland Hospital for Psychogeriatric Medicine

85

Neuropsychologist

01/2006 – 06/2006 Psychiatric University Hospital Zurich, Switzerland Ward for Dual Diagnoses Patients

Assistant Clinical Psychologist PUBLICATIONS Schlumpf, Y.R., Nijenhuis, E.R.S., Chalavi, S., Weder, E.V., Zimmermann, E., Lüchinger, R., La Marca, R., Reinders, A.A.T.S., & Jäncke, L. (2013). Dissociative part-dependent biopsychosocial reactions to backward masked angry and neutral faces: An fMRI study of dissociative identity disorder. NeuroImage: Clinical, 3, 54-64. Schlumpf, Y.R., Reinders, A.A.T.S., Nijenhuis, E.R.S., Lüchinger, R., Van Osch, M.J.P, & Jäncke, L. (in preparation). Dissociative part-dependent resting-state activity: A controlled fMRI perfusion study of dissociative identity disorder. INVITED TALKS Schlumpf, Y.R. (2010, Januar). MRT-Studie mit DIS-Patienten. ESTD-Tagung, Universität Bern, Bern. Schlumpf, Y.R. (2011, November). Gibt es Multiple Persönlichkeiten? Aktuelle biopsychologische Befunde. 3. Dialogtagung der Arbeitsgemeinschaft für Verhaltensmodifikation Schweiz (AVM-CH), Epilepsie-Klinik, Zürich. Schlumpf, Y.R. (2012, Januar). Vorbewusste mentale Vermeidung von bedrohlichen Reizen. Eine fMRT-Studie mit DIS-Patienten. ESTD-Tagung, Universität Bern, Bern. POSTER/ABSTRACTS Schlumpf, Y.R., Nijenhuis, E.R.S., Chalavi, S., Weder, E.V., Zimmermann, E., Reinders, A.A.T.S., & Jäncke, L. (2011, November). Preconscious processing of perceived threat in patients with a dissociative identity disorder. An fMRI study. Poster presented at the 28th ISSTD Annual Conference, Montréal, Canada. Schlumpf, Y.R., Nijenhuis, E.R.S., & Weder, E.V. (March, 2012). Psychobiological reactions to masked neutral and angry faces: A controlled functional MRI study of dissociative identity disorder. Talk given at the 3rd ESTD Bi-Annual Conference, Berlin, Germany. Schlumpf, Y.R., Nijenhuis, E.R.S., Chalavi, S., Weder, E.V., Zimmermann, E., Lüchinger, R., La Marca, R., Reinders, A.A.T.S., & Jäncke, L. (June, 2012). Preconscious processing of perceived threat in patients with a Dissociative Identity Disorder. An fMRI study. Poster presented at the ZNZ Symposium, Zurich,

86

Switzerland. TEACHING Spring semester 2012 Lecturing the MSc programme in Neurobiology of

psychiatric disorders Spring semester 2012 Workshop in Neurobiology of dissociative identity

disorder SUPERVISION OF UNDERGRADUATE STUDENTS 2009 – present 5 BSc students

2 MSc students RESEARCH GRANTS 07/2009 – 04/2012 Forschungskredit, University of Zurich

the brain in dissociative identity disorder : reactions to ... · dissociative identity disorder...

Documents